Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.8
4.4
Journals
Cancers
Editor’s Choice
cancers-logo

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

Order results
Result details
Results per page
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Review

25 pages, 1410 KiB  
Review
The Cell Biology of Metastatic Invasion in Pancreatic Cancer: Updates and Mechanistic Insights
by Vidhu B. Joshi, Omar L. Gutierrez Ruiz and Gina L. Razidlo
Cancers 2023, 15(7), 2169; https://doi.org/10.3390/cancers15072169 - 6 Apr 2023
Cited by 12 | Viewed by 5737
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality worldwide. This is largely due to the lack of routine screening protocols, an absence of symptoms in early-stage disease leading to late detection, and a paucity of effective treatment options. [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality worldwide. This is largely due to the lack of routine screening protocols, an absence of symptoms in early-stage disease leading to late detection, and a paucity of effective treatment options. Critically, the majority of patients either present with metastatic disease or rapidly develop metastatic disease. Thus, there is an urgent need to deepen our understanding of metastasis in PDAC. During metastasis, tumor cells escape from the primary tumor, enter the circulation, and travel to a distant site to form a secondary tumor. In order to accomplish this relatively rare event, tumor cells develop an enhanced ability to detach from the primary tumor, migrate into the surrounding matrix, and invade across the basement membrane. In addition, cancer cells interact with the various cell types and matrix proteins that comprise the tumor microenvironment, with some of these factors working to promote metastasis and others working to suppress it. In PDAC, many of these processes are not well understood. The purpose of this review is to highlight recent advances in the cell biology of the early steps of the metastatic cascade in pancreatic cancer. Specifically, we will examine the regulation of epithelial-to-mesenchymal transition (EMT) in PDAC and its requirement for metastasis, summarize our understanding of how PDAC cells invade and degrade the surrounding matrix, and discuss how migration and adhesion dynamics are regulated in PDAC to optimize cancer cell motility. In addition, the role of the tumor microenvironment in PDAC will also be discussed for each of these invasive processes. Full article
(This article belongs to the Collection Recent Advances in Pancreatic Ductal Adenocarcinoma)
►▼ Show Figures

Figure 1

20 pages, 1020 KiB  
Review
Detection and Molecular Characterization of Circulating Tumour Cells: Challenges for the Clinical Setting
by Areti Strati, Athina Markou, Evgenia Kyriakopoulou and Evi Lianidou
Cancers 2023, 15(7), 2185; https://doi.org/10.3390/cancers15072185 - 6 Apr 2023
Cited by 22 | Viewed by 4735
Abstract
Over the last decade, liquid biopsy has gained much attention as a powerful tool in personalized medicine since it enables monitoring cancer evolution and follow-up of cancer patients in real time. Through minimally invasive procedures, liquid biopsy provides important information through the analysis [...] Read more.
Over the last decade, liquid biopsy has gained much attention as a powerful tool in personalized medicine since it enables monitoring cancer evolution and follow-up of cancer patients in real time. Through minimally invasive procedures, liquid biopsy provides important information through the analysis of circulating tumour cells (CTCs) and circulating tumour-derived material, such as circulating tumour DNA (ctDNA), circulating miRNAs (cfmiRNAs) and extracellular vehicles (EVs). CTC analysis has already had an important impact on the prognosis, detection of minimal residual disease (MRD), treatment selection and monitoring of cancer patients. Numerous clinical trials nowadays include a liquid biopsy arm. CTC analysis is now an exponentially expanding field in almost all types of solid cancers. Functional studies, mainly based on CTC-derived cell-lines and CTC-derived explants (CDx), provide important insights into the metastatic process. The purpose of this review is to summarize the latest findings on the clinical significance of CTCs for the management of cancer patients, covering the last four years. This review focuses on providing a comprehensive overview of CTC analysis in breast, prostate and non-small-cell lung cancer. The unique potential of CTC single-cell analysis for understanding metastasis biology, and the importance of quality control and standardization of methodologies used in this field, is also discussed. Full article
(This article belongs to the Special Issue The 5th ACTC: “Liquid Biopsy in Its Best”)
►▼ Show Figures

Figure 1

58 pages, 2391 KiB  
Review
DNA-Based Nanomaterials as Drug Delivery Platforms for Increasing the Effect of Drugs in Tumors
by Anastasiya N. Shishparenok, Vitalina V. Furman and Dmitry D. Zhdanov
Cancers 2023, 15(7), 2151; https://doi.org/10.3390/cancers15072151 - 5 Apr 2023
Cited by 23 | Viewed by 6619
Abstract
DNA nanotechnology has significantly advanced and might be used in biomedical applications, drug delivery, and cancer treatment during the past few decades. DNA nanomaterials are widely used in biomedical research involving biosensing, bioimaging, and drug delivery since they are remarkably addressable and biocompatible. [...] Read more.
DNA nanotechnology has significantly advanced and might be used in biomedical applications, drug delivery, and cancer treatment during the past few decades. DNA nanomaterials are widely used in biomedical research involving biosensing, bioimaging, and drug delivery since they are remarkably addressable and biocompatible. Gradually, modified nucleic acids have begun to be employed to construct multifunctional DNA nanostructures with a variety of architectural designs. Aptamers are single-stranded nucleic acids (both DNAs and RNAs) capable of self-pairing to acquire secondary structure and of specifically binding with the target. Diagnosis and tumor therapy are prospective fields in which aptamers can be applied. Many DNA nanomaterials with three-dimensional structures have been studied as drug delivery systems for different anticancer medications or gene therapy agents. Different chemical alterations can be employed to construct a wide range of modified DNA nanostructures. Chemically altered DNA-based nanomaterials are useful for drug delivery because of their improved stability and inclusion of functional groups. In this work, the most common oligonucleotide nanomaterials were reviewed as modern drug delivery systems in tumor cells. Full article
(This article belongs to the Special Issue Nanoplatforms Based Cancers Therapy 2.0)
►▼ Show Figures

Graphical abstract

37 pages, 1753 KiB  
Review
Mechanisms of Resistance and Current Treatment Options for Glioblastoma Multiforme (GBM)
by Satya Siva Kishan Yalamarty, Nina Filipczak, Xiang Li, Md Abdus Subhan, Farzana Parveen, Janaína Artem Ataide, Bharat Ashok Rajmalani and Vladimir P. Torchilin
Cancers 2023, 15(7), 2116; https://doi.org/10.3390/cancers15072116 - 1 Apr 2023
Cited by 121 | Viewed by 16704
Abstract
Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer that is difficult to treat due to its resistance to both radiation and chemotherapy. This resistance is largely due to the unique biology of GBM cells, which can evade the effects of [...] Read more.
Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer that is difficult to treat due to its resistance to both radiation and chemotherapy. This resistance is largely due to the unique biology of GBM cells, which can evade the effects of conventional treatments through mechanisms such as increased resistance to cell death and rapid regeneration of cancerous cells. Additionally, the blood–brain barrier makes it difficult for chemotherapy drugs to reach GBM cells, leading to reduced effectiveness. Despite these challenges, there are several treatment options available for GBM. The standard of care for newly diagnosed GBM patients involves surgical resection followed by concurrent chemoradiotherapy and adjuvant chemotherapy. Emerging treatments include immunotherapy, such as checkpoint inhibitors, and targeted therapies, such as bevacizumab, that attempt to attack specific vulnerabilities in GBM cells. Another promising approach is the use of tumor-treating fields, a type of electric field therapy that has been shown to slow the growth of GBM cells. Clinical trials are ongoing to evaluate the safety and efficacy of these and other innovative treatments for GBM, intending to improve with outcomes for patients. Full article
►▼ Show Figures

Graphical abstract

30 pages, 1692 KiB  
Review
The Glioma Immune Landscape: A Double-Edged Sword for Treatment Regimens
by Sukrit Mahajan, Mirko H. H. Schmidt and Ulrike Schumann
Cancers 2023, 15(7), 2024; https://doi.org/10.3390/cancers15072024 - 28 Mar 2023
Cited by 16 | Viewed by 4960
Abstract
Immune cells constitute a major part of the tumor microenvironment, thereby playing an important role in regulating tumor development. They interact with tumor cells, resulting in the suppression or promotion of glioma development. Therefore, in recent years, scientists have focused on immunotherapy that [...] Read more.
Immune cells constitute a major part of the tumor microenvironment, thereby playing an important role in regulating tumor development. They interact with tumor cells, resulting in the suppression or promotion of glioma development. Therefore, in recent years, scientists have focused on immunotherapy that involves enhancing the immune response to fight the battle against cancer more effectively. While it has shown success against different cancer types, immunotherapy faces major roadblocks in glioma treatment. These involve the blood brain barrier, tumor heterogeneity and an immunosuppressive glioma microenvironment, among other factors. Additionally, the interaction of the peripheral immune system with the central nervous system provides another challenge for immunotherapeutic regimens. For modulating different immune cell populations to counter glioma cells, it is important to expand our knowledge about their role within the glioma microenvironment; therefore, herein, we review the different immune cell populations found in the glioma microenvironment and navigate through the various shortcomings of current immunotherapies for glioma. We conclude by providing an insight into ongoing pre-clinical and clinical trials for glioma therapies. Full article
(This article belongs to the Special Issue The Development of Effective Therapy Targeting the Microenvironment of Cancer)
►▼ Show Figures

Figure 1

18 pages, 3732 KiB  
Review
Treatment Strategies for KRAS-Mutated Non-Small-Cell Lung Cancer
by Éabha O’Sullivan, Anna Keogh, Brian Henderson, Stephen P. Finn, Steven G. Gray and Kathy Gately
Cancers 2023, 15(6), 1635; https://doi.org/10.3390/cancers15061635 - 7 Mar 2023
Cited by 49 | Viewed by 14006
Abstract
Activating mutations in KRAS are highly prevalent in solid tumours and are frequently found in 35% of lung, 45% of colorectal, and up to 90% of pancreatic cancers. Mutated KRAS is a prognostic factor for disease-free survival (DFS) and overall survival (OS) in [...] Read more.
Activating mutations in KRAS are highly prevalent in solid tumours and are frequently found in 35% of lung, 45% of colorectal, and up to 90% of pancreatic cancers. Mutated KRAS is a prognostic factor for disease-free survival (DFS) and overall survival (OS) in NSCLC and is associated with a more aggressive clinical phenotype, highlighting the need for KRAS-targeted therapy. Once considered undruggable due to its smooth shallow surface, a breakthrough showed that the activated G12C-mutated KRAS isozyme can be directly inhibited via a newly identified switch II pocket. This discovery led to the development of a new class of selective small-molecule inhibitors against the KRAS G12C isoform. Sotorasib and adagrasib are approved in locally advanced or metastatic NSCLC patients who have received at least one prior systemic therapy. Currently, there are at least twelve KRAS G12C inhibitors being tested in clinical trials, either as a single agent or in combination. In this study, KRAS mutation prevalence, subtypes, rates of occurrence in treatment-resistant invasive mucinous adenocarcinomas (IMAs), and novel drug delivery options are reviewed. Additionally, the current status of KRAS inhibitors, multiple resistance mechanisms that limit efficacy, and their use in combination treatment strategies and novel multitargeted approaches in NSCLC are discussed. Full article
(This article belongs to the Special Issue Update in Lung Cancer Molecular Pathology: Technological Advances and Clinical Practice)
►▼ Show Figures

Figure 1

85 pages, 4243 KiB  
Review
The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer—Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy
by Katarzyna Starska-Kowarska
Cancers 2023, 15(6), 1642; https://doi.org/10.3390/cancers15061642 - 7 Mar 2023
Cited by 24 | Viewed by 10102
Abstract
Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive and heterogeneous groups of human neoplasms. HNSCC is characterized by high morbidity, accounting for 3% of all cancers, and high mortality with ~1.5% of all cancer deaths. It was the [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive and heterogeneous groups of human neoplasms. HNSCC is characterized by high morbidity, accounting for 3% of all cancers, and high mortality with ~1.5% of all cancer deaths. It was the most common cancer worldwide in 2020, according to the latest GLOBOCAN data, representing the seventh most prevalent human malignancy. Despite great advances in surgical techniques and the application of modern combinations and cytotoxic therapies, HNSCC remains a leading cause of death worldwide with a low overall survival rate not exceeding 40–60% of the patient population. The most common causes of death in patients are its frequent nodal metastases and local neoplastic recurrences, as well as the relatively low response to treatment and severe drug resistance. Much evidence suggests that the tumour microenvironment (TME), tumour infiltrating lymphocytes (TILs) and circulating various subpopulations of immunocompetent cells, such regulatory T cells (CD4+CD25+Foxp3+Tregs), cytotoxic CD3+CD8+ T cells (CTLs) and CD3+CD4+ T helper type 1/2/9/17 (Th1/Th2/Th9/Th17) lymphocytes, T follicular helper cells (Tfh) and CD56dim/CD16bright activated natural killer cells (NK), carcinoma-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (N1/N2 TANs), as well as tumour-associated macrophages (M1/M2 phenotype TAMs) can affect initiation, progression and spread of HNSCC and determine the response to immunotherapy. Rapid advances in the field of immuno-oncology and the constantly growing knowledge of the immunosuppressive mechanisms and effects of tumour cancer have allowed for the use of effective and personalized immunotherapy as a first-line therapeutic procedure or an essential component of a combination therapy for primary, relapsed and metastatic HNSCC. This review presents the latest reports and molecular studies regarding the anti-tumour role of selected subpopulations of immunocompetent cells in the pathogenesis of HNSCC, including HPV+ve (HPV+) and HPV−ve (HPV−) tumours. The article focuses on the crucial regulatory mechanisms of pro- and anti-tumour activity, key genetic or epigenetic changes that favour tumour immune escape, and the strategies that the tumour employs to avoid recognition by immunocompetent cells, as well as resistance mechanisms to T and NK cell-based immunotherapy in HNSCC. The present review also provides an overview of the pre- and clinical early trials (I/II phase) and phase-III clinical trials published in this arena, which highlight the unprecedented effectiveness and limitations of immunotherapy in HNSCC, and the emerging issues facing the field of HNSCC immuno-oncology. Full article
(This article belongs to the Special Issue Molecular Signatures in Head and Neck Cancer)
►▼ Show Figures

Figure 1

35 pages, 1829 KiB  
Review
Immunotargeting of Cancer Stem Cells
by Ayse Sedef Köseer, Simona Di Gaetano, Claudia Arndt, Michael Bachmann and Anna Dubrovska
Cancers 2023, 15(5), 1608; https://doi.org/10.3390/cancers15051608 - 5 Mar 2023
Cited by 14 | Viewed by 5006
Abstract
The generally accepted view is that CSCs hijack the signaling pathways attributed to normal stem cells that regulate the self-renewal and differentiation processes. Therefore, the development of selective targeting strategies for CSC, although clinically meaningful, is associated with significant challenges because CSC and [...] Read more.
The generally accepted view is that CSCs hijack the signaling pathways attributed to normal stem cells that regulate the self-renewal and differentiation processes. Therefore, the development of selective targeting strategies for CSC, although clinically meaningful, is associated with significant challenges because CSC and normal stem cells share many important signaling mechanisms for their maintenance and survival. Furthermore, the efficacy of this therapy is opposed by tumor heterogeneity and CSC plasticity. While there have been considerable efforts to target CSC populations by the chemical inhibition of the developmental pathways such as Notch, Hedgehog (Hh), and Wnt/β-catenin, noticeably fewer attempts were focused on the stimulation of the immune response by CSC-specific antigens, including cell-surface targets. Cancer immunotherapies are based on triggering the anti-tumor immune response by specific activation and targeted redirecting of immune cells toward tumor cells. This review is focused on CSC-directed immunotherapeutic approaches such as bispecific antibodies and antibody-drug candidates, CSC-targeted cellular immunotherapies, and immune-based vaccines. We discuss the strategies to improve the safety and efficacy of the different immunotherapeutic approaches and describe the current state of their clinical development. Full article
(This article belongs to the Special Issue Cancer Stem Cells and Targeted Therapy)
►▼ Show Figures

Graphical abstract

23 pages, 370 KiB  
Review
Bispecific T-Cell Engagers Therapies in Solid Tumors: Focusing on Prostate Cancer
by Diana C. Simão, Kevin K. Zarrabi, José L. Mendes, Ricardo Luz, Jorge A. Garcia, William K. Kelly and Pedro C. Barata
Cancers 2023, 15(5), 1412; https://doi.org/10.3390/cancers15051412 - 23 Feb 2023
Cited by 30 | Viewed by 8304
Abstract
Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering [...] Read more.
Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering responses. Similarly, many tumors’ immune microenvironment allows them to become evasive, leading to resistance and, thus, limiting the durability of responses. To overcome this limitation, new T-cell redirecting strategies such as bispecific T-cell engager (BiTE) have become attractive and promising immunotherapies. Our review provides a comprehensive perspective of the current evidence of BiTE therapies in solid tumors. Considering that immunotherapy has shown modest results in advanced prostate cancer to date, we review the biologic rationale and promising results of BiTE therapy in this clinical setting and discuss potential tumor-associated antigens that may be integrated into BiTE construct designs. Our review also aims to evaluate the advances of BiTE therapies in prostate cancer, illustrate the major obstacles and underlying limitations, and discuss directions for future research. Full article
(This article belongs to the Collection Urological Cancer 2023-2025)
16 pages, 1929 KiB  
Review
Unlocking the Resistance to Anti-HER2 Treatments in Breast Cancer: The Issue of HER2 Spatial Distribution
by Federica Giugliano, Ambra Carnevale Schianca, Chiara Corti, Mariia Ivanova, Nadia Bianco, Silvia Dellapasqua, Carmen Criscitiello, Nicola Fusco, Giuseppe Curigliano and Elisabetta Munzone
Cancers 2023, 15(5), 1385; https://doi.org/10.3390/cancers15051385 - 22 Feb 2023
Cited by 14 | Viewed by 5597
Abstract
Approximately 15% of breast cancers are classified as HER2-positive, with an amplification of the ERBB2 gene and/or an overexpression of the HER2 protein. Up to 30% of HER2-positive breast cancers shows heterogeneity in HER2 expression and different patterns of spatial distribution, i.e., the [...] Read more.
Approximately 15% of breast cancers are classified as HER2-positive, with an amplification of the ERBB2 gene and/or an overexpression of the HER2 protein. Up to 30% of HER2-positive breast cancers shows heterogeneity in HER2 expression and different patterns of spatial distribution, i.e., the variability in the distribution and expression of the HER2 protein within a single tumour. Spatial heterogeneity may potentially affect treatment, response, assessment of HER2 status and consequently, may impact on the best treatment strategy. Understanding this feature can help clinicians to predict response to HER2-targeted therapies and patient outcomes, and to fine tune treatment decisions. This review summarizes the available evidence on HER2 heterogeneity and spatial distribution and how this may affect current available treatment choices, exploring possible opportunities for overcoming this issue, such as novel pharmacological agents, belonging to the group of antibody–drug conjugates. Full article
(This article belongs to the Special Issue Anti-HER2 Therapy Resistance in Breast Cancer)
►▼ Show Figures

Figure 1

14 pages, 1198 KiB  
Review
The Gut-Prostate Axis: A New Perspective of Prostate Cancer Biology through the Gut Microbiome
by Kazutoshi Fujita, Makoto Matsushita, Marco A. De Velasco, Koji Hatano, Takafumi Minami, Norio Nonomura and Hirotsugu Uemura
Cancers 2023, 15(5), 1375; https://doi.org/10.3390/cancers15051375 - 21 Feb 2023
Cited by 30 | Viewed by 6680
Abstract
Obesity and a high-fat diet are risk factors associated with prostate cancer, and lifestyle, especially diet, impacts the gut microbiome. The gut microbiome plays important roles in the development of several diseases, such as Alzheimer’s disease, rheumatoid arthritis, and colon cancer. The analysis [...] Read more.
Obesity and a high-fat diet are risk factors associated with prostate cancer, and lifestyle, especially diet, impacts the gut microbiome. The gut microbiome plays important roles in the development of several diseases, such as Alzheimer’s disease, rheumatoid arthritis, and colon cancer. The analysis of feces from patients with prostate cancer by 16S rRNA sequencing has uncovered various associations between altered gut microbiomes and prostate cancer. Gut dysbiosis caused by the leakage of gut bacterial metabolites, such as short-chain fatty acids and lipopolysaccharide results in prostate cancer growth. Gut microbiota also play a role in the metabolism of androgen which could affect castration-resistant prostate cancer. Moreover, men with high-risk prostate cancer share a specific gut microbiome and treatments such as androgen-deprivation therapy alter the gut microbiome in a manner that favors prostate cancer growth. Thus, implementing interventions aiming to modify lifestyle or altering the gut microbiome with prebiotics or probiotics may curtail the development of prostate cancer. From this perspective, the “Gut–Prostate Axis” plays a fundamental bidirectional role in prostate cancer biology and should be considered when screening and treating prostate cancer patients. Full article
(This article belongs to the Special Issue Metastatic Prostate Cancer: Interaction with Tumors and Their Microenvironments)
►▼ Show Figures

Figure 1

23 pages, 1809 KiB  
Review
Downstream Targets of VHL/HIF-α Signaling in Renal Clear Cell Carcinoma Progression: Mechanisms and Therapeutic Relevance
by Sonia Mazumder, Paul J. Higgins and Rohan Samarakoon
Cancers 2023, 15(4), 1316; https://doi.org/10.3390/cancers15041316 - 19 Feb 2023
Cited by 43 | Viewed by 9308
Abstract
The clear cell variant of renal cell carcinoma (ccRCC) is the most common renal epithelial malignancy and responsible for most of the deaths from kidney cancer. Patients carrying inactivating mutations in the Von Hippel-Lindau (VHL) gene have an increased proclivity to develop several [...] Read more.
The clear cell variant of renal cell carcinoma (ccRCC) is the most common renal epithelial malignancy and responsible for most of the deaths from kidney cancer. Patients carrying inactivating mutations in the Von Hippel-Lindau (VHL) gene have an increased proclivity to develop several types of tumors including ccRCC. Normally, the Hypoxia Inducible Factor alpha (HIF-α) subunits of the HIF heterodimeric transcription factor complex are regulated by oxygen-dependent prolyl-hydroxylation, VHL-mediated ubiquitination and proteasomal degradation. Loss of pVHL function results in elevated levels of HIF-α due to increased stability, leading to RCC progression. While HIF-1α acts as a tumor suppressor, HIF-2α promotes oncogenic potential by driving tumor progression and metastasis through activation of hypoxia-sensitive signaling pathways and overexpression of HIF-2α target genes. One strategy to suppress ccRCC aggressiveness is directed at inhibition of HIF-2α and the associated molecular pathways leading to cell proliferation, angiogenesis, and metastasis. Indeed, clinical and pre-clinical data demonstrated the effectiveness of HIF-2α targeted therapy in attenuating ccRCC progression. This review focuses on the signaling pathways and the involved genes (cyclin D, c-Myc, VEGF-a, EGFR, TGF-α, GLUT-1) that confer oncogenic potential downstream of the VHL-HIF-2α signaling axis in ccRCC. Discussed as well are current treatment options (including receptor tyrosine kinase inhibitors such as sunitinib), the medical challenges (high prevalence of metastasis at the time of diagnosis, refractory nature of advanced disease to current treatment options), scientific challenges and future directions. Full article
(This article belongs to the Special Issue Cancers Driven by HIF)
►▼ Show Figures

Figure 1

12 pages, 1341 KiB  
Review
Mechanisms of Resistance to Antibody–Drug Conjugates
by Rachel Occhiogrosso Abelman, Bogang Wu, Laura M. Spring, Leif W. Ellisen and Aditya Bardia
Cancers 2023, 15(4), 1278; https://doi.org/10.3390/cancers15041278 - 17 Feb 2023
Cited by 67 | Viewed by 8847
Abstract
Antibody–drug conjugates (ADCs), with antibodies targeted against specific antigens linked to cytotoxic payloads, offer the opportunity for a more specific delivery of chemotherapy and other bioactive payloads to minimize side effects. First approved in the setting of HER2+ breast cancer, more recent ADCs [...] Read more.
Antibody–drug conjugates (ADCs), with antibodies targeted against specific antigens linked to cytotoxic payloads, offer the opportunity for a more specific delivery of chemotherapy and other bioactive payloads to minimize side effects. First approved in the setting of HER2+ breast cancer, more recent ADCs have been developed for triple-negative breast cancer (TNBC) and, most recently, hormone receptor-positive (HR+) breast cancer. While antibody–drug conjugates have compared favorably against traditional chemotherapy in some settings, patients eventually progress on these therapies and require a change in treatment. Mechanisms to explain the resistance to ADCs are highly sought after, in hopes of developing next-line treatment options and expanding the therapeutic windows of existing therapies. These resistance mechanisms are categorized as follows: change in antigen expression, change in ADC processing and resistance, and efflux of the ADC payload. This paper reviews the recently published literature on these mechanisms as well as potential options to overcome these barriers. Full article
(This article belongs to the Special Issue Resistance in Breast Cancer)
►▼ Show Figures

Figure 1

12 pages, 293 KiB  
Review
Evolving Treatment Landscape of HER2-mutant Non-Small Cell Lung Cancer: Trastuzumab Deruxtecan and Beyond
by Ioannis A. Vathiotis, Dimitrios Bafaloukos, Konstantinos N. Syrigos and George Samonis
Cancers 2023, 15(4), 1286; https://doi.org/10.3390/cancers15041286 - 17 Feb 2023
Cited by 14 | Viewed by 4462
Abstract
Successful targeting of HER2-activating mutations in DESTINY-Lung02 phase II study has led to the approval of the antibody–drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) as second-line treatment in patients with non-small cell lung cancer (NSCLC). Despite the impressive results, several matters need to [...] Read more.
Successful targeting of HER2-activating mutations in DESTINY-Lung02 phase II study has led to the approval of the antibody–drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) as second-line treatment in patients with non-small cell lung cancer (NSCLC). Despite the impressive results, several matters need to be addressed, including the clinical activity of T-DXd in patients with disease in the central nervous system as well as the role of T-DXd in the context of HER2 overexpression. Additionally, data regarding novel agents used to target HER2 continue to accumulate. This review highlights the challenges and unanswered questions that have emerged after the approval of T-DXd in patients with HER2-mutant NSCLC. Full article
(This article belongs to the Special Issue World Lung Cancer Awareness Month)
12 pages, 862 KiB  
Review
CAR-T Therapy in GBM: Current Challenges and Avenues for Improvement
by Ayush Pant and Michael Lim
Cancers 2023, 15(4), 1249; https://doi.org/10.3390/cancers15041249 - 16 Feb 2023
Cited by 20 | Viewed by 4924
Abstract
Completed clinical trials of CAR-T cells in glioblastoma (GBM) have revealed key challenges that limit their efficacy. These include incomplete antigen coverage, downregulation of target antigen in response to therapy, exposure to immunosuppressive cells and cytokines in the tumor microenvironment and exhaustion of [...] Read more.
Completed clinical trials of CAR-T cells in glioblastoma (GBM) have revealed key challenges that limit their efficacy. These include incomplete antigen coverage, downregulation of target antigen in response to therapy, exposure to immunosuppressive cells and cytokines in the tumor microenvironment and exhaustion of CAR-T cells. To overcome these challenges, CAR-T cells have been modified to maximize effector function and resist immunosuppression in the tumor while limiting toxicities to the host. Adoption of these novel CAR-T strategies in GBM can overcome the “cold tumor” phenotype of GBM and trigger an inflammatory cascade that maximizes tumor clearance and minimizes CAR-T dysfunction. To achieve this, understanding and harnessing the antigenic, metabolic and immunological composition of GBM is crucial. Here we review the findings from completed clinical trials of CAR-T cells in GBM as well as novel strategies that could improve CAR-T survival and function in the tumor. Full article
(This article belongs to the Collection Treatment of Glioma)
►▼ Show Figures

Figure 1

21 pages, 2645 KiB  
Review
NKG2A Immune Checkpoint in Vδ2 T Cells: Emerging Application in Cancer Immunotherapy
by Valentina Cazzetta, Delphine Depierreux, Francesco Colucci, Joanna Mikulak and Domenico Mavilio
Cancers 2023, 15(4), 1264; https://doi.org/10.3390/cancers15041264 - 16 Feb 2023
Cited by 9 | Viewed by 5076
Abstract
Immune regulation has revolutionized cancer treatment with the introduction of T-cell-targeted immune checkpoint inhibitors (ICIs). This successful immunotherapy has led to a more complete view of cancer that now considers not only the cancer cells to be targeted and destroyed but also the [...] Read more.
Immune regulation has revolutionized cancer treatment with the introduction of T-cell-targeted immune checkpoint inhibitors (ICIs). This successful immunotherapy has led to a more complete view of cancer that now considers not only the cancer cells to be targeted and destroyed but also the immune environment of the cancer cells. Current challenges associated with the enhancement of ICI effects are increasing the fraction of responding patients through personalized combinations of multiple ICIs and overcoming acquired resistance. This requires a complete overview of the anti-tumor immune response, which depends on a complex interplay between innate and adaptive immune cells with the tumor microenvironment. The NKG2A was revealed to be a key immune checkpoint for both Natural Killer (NK) cells and T cells. Monalizumab, a humanized anti-NKG2A antibody, enhances NK cell activity against various tumor cells and rescues CD8 αβ T cell function in combination with PD-1/PD-L1 blockade. In this review, we discuss the potential for targeting NKG2A expressed on tumor-sensing human γδ T cells, mostly on the specific Vδ2 T cell subset, in order to emphasize its importance and potential in the development of new ICI-based therapeutic approaches. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
►▼ Show Figures

Figure 1

28 pages, 1165 KiB  
Review
Hypoxia, a Targetable Culprit to Counter Pancreatic Cancer Resistance to Therapy
by Raefa Abou Khouzam, Jean-Marie Lehn, Hemma Mayr, Pierre-Alain Clavien, Michael Bradley Wallace, Michel Ducreux, Perparim Limani and Salem Chouaib
Cancers 2023, 15(4), 1235; https://doi.org/10.3390/cancers15041235 - 15 Feb 2023
Cited by 14 | Viewed by 4695
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and it is a disease of dismal prognosis. While immunotherapy has revolutionized the treatment of various solid tumors, it has achieved little success in PDAC. Hypoxia within the stroma-rich tumor microenvironment [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and it is a disease of dismal prognosis. While immunotherapy has revolutionized the treatment of various solid tumors, it has achieved little success in PDAC. Hypoxia within the stroma-rich tumor microenvironment is associated with resistance to therapies and promotes angiogenesis, giving rise to a chaotic and leaky vasculature that is inefficient at shuttling oxygen and nutrients. Hypoxia and its downstream effectors have been implicated in immune resistance and could be contributing to the lack of response to immunotherapy experienced by patients with PDAC. Paradoxically, increasing evidence has shown hypoxia to augment genomic instability and mutagenesis in cancer, suggesting that hypoxic tumor cells could have increased production of neoantigens that can potentially enable their clearance by cytotoxic immune cells. Strategies aimed at relieving this condition have been on the rise, and one such approach opts for normalizing the tumor vasculature to reverse hypoxia and its downstream support of tumor pathogenesis. An important consideration for the successful implementation of such strategies in the clinic is that not all PDACs are equally hypoxic, therefore hypoxia-detection approaches should be integrated to enable optimal patient selection for achieving improved patient outcomes. Full article
(This article belongs to the Collection Recent Advances in Pancreatic Ductal Adenocarcinoma)
►▼ Show Figures

Figure 1

25 pages, 775 KiB  
Review
Radiomics Applications in Head and Neck Tumor Imaging: A Narrative Review
by Mario Tortora, Laura Gemini, Alessandra Scaravilli, Lorenzo Ugga, Andrea Ponsiglione, Arnaldo Stanzione, Felice D’Arco, Gennaro D’Anna and Renato Cuocolo
Cancers 2023, 15(4), 1174; https://doi.org/10.3390/cancers15041174 - 12 Feb 2023
Cited by 29 | Viewed by 4377
Abstract
Recent advances in machine learning and artificial intelligence technology have ensured automated evaluation of medical images. As a result, quantifiable diagnostic and prognostic biomarkers have been created. We discuss radiomics applications for the head and neck region in this paper. Molecular characterization, categorization, [...] Read more.
Recent advances in machine learning and artificial intelligence technology have ensured automated evaluation of medical images. As a result, quantifiable diagnostic and prognostic biomarkers have been created. We discuss radiomics applications for the head and neck region in this paper. Molecular characterization, categorization, prognosis and therapy recommendation are given special consideration. In a narrative manner, we outline the fundamental technological principles, the overall idea and usual workflow of radiomic analysis and what seem to be the present and potential challenges in normal clinical practice. Clinical oncology intends for all of this to ensure informed decision support for personalized and useful cancer treatment. Head and neck cancers present a unique set of diagnostic and therapeutic challenges. These challenges are brought on by the complicated anatomy and heterogeneity of the area under investigation. Radiomics has the potential to address these barriers. Future research must be interdisciplinary and focus on the study of certain oncologic functions and outcomes, with external validation and multi-institutional cooperation in order to achieve this. Full article
►▼ Show Figures

Figure 1

27 pages, 471 KiB  
Review
CAR-Based Immunotherapy of Solid Tumours—A Survey of the Emerging Targets
by John Maher and David M. Davies
Cancers 2023, 15(4), 1171; https://doi.org/10.3390/cancers15041171 - 11 Feb 2023
Cited by 19 | Viewed by 7210
Abstract
Immunotherapy with CAR T-cells has revolutionised the treatment of B-cell and plasma cell-derived cancers. However, solid tumours present a much greater challenge for treatment using CAR-engineered immune cells. In a partner review, we have surveyed data generated in clinical trials in which patients [...] Read more.
Immunotherapy with CAR T-cells has revolutionised the treatment of B-cell and plasma cell-derived cancers. However, solid tumours present a much greater challenge for treatment using CAR-engineered immune cells. In a partner review, we have surveyed data generated in clinical trials in which patients with solid tumours that expressed any of 30 discrete targets were treated with CAR-based immunotherapy. That exercise confirms that efficacy of this approach falls well behind that seen in haematological malignancies, while significant toxic events have also been reported. Here, we consider approximately 60 additional candidates for which such clinical data are not available yet, but where pre-clinical data have provided support for their advancement to clinical evaluation as CAR target antigens. Full article
►▼ Show Figures

Graphical abstract

31 pages, 1969 KiB  
Review
Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy
by Hafiza Padinharayil, Vikrant Rai and Alex George
Cancers 2023, 15(4), 1070; https://doi.org/10.3390/cancers15041070 - 8 Feb 2023
Cited by 10 | Viewed by 4240
Abstract
Pancreatic ductal adenocarcinoma (PDAC), the fourteenth most common malignancy, is a major contributor to cancer-related death with the utmost case fatality rate among all malignancies. Functional mitochondria, regardless of their complex ecosystem relative to normal cells, are essential in PDAC progression. Tumor cells’ [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC), the fourteenth most common malignancy, is a major contributor to cancer-related death with the utmost case fatality rate among all malignancies. Functional mitochondria, regardless of their complex ecosystem relative to normal cells, are essential in PDAC progression. Tumor cells’ potential to produce ATP as energy, despite retaining the redox potential optimum, and allocating materials for biosynthetic activities that are crucial for cell growth, survival, and proliferation, are assisted by mitochondria. The polyclonal tumor cells with different metabolic profiles may add to carcinogenesis through inter-metabolic coupling. Cancer cells frequently possess alterations in the mitochondrial genome, although they do not hinder metabolism; alternatively, they change bioenergetics. This can further impart retrograde signaling, educate cell signaling, epigenetic modifications, chromatin structures, and transcription machinery, and ultimately satisfy cancer cellular and nuclear demands. To maximize the tumor microenvironment (TME), tumor cells remodel nearby stromal cells and extracellular matrix. These changes initiate polyclonality, which is crucial for growth, stress response, and metastasis. Here, we evaluate all the intrinsic and extrinsic pathways drawn by mitochondria in carcinogenesis, emphasizing the perspectives of mitochondrial metabolism in PDAC progression and treatment. Full article
(This article belongs to the Special Issue Mitochondria and Metabolism of Pancreatic Adenocarcinoma Cells)
►▼ Show Figures

Figure 1

23 pages, 3095 KiB  
Review
Aquaporins and Ion Channels as Dual Targets in the Design of Novel Glioblastoma Therapeutics to Limit Invasiveness
by Alanah Varricchio and Andrea J. Yool
Cancers 2023, 15(3), 849; https://doi.org/10.3390/cancers15030849 - 30 Jan 2023
Cited by 4 | Viewed by 4332
Abstract
Current therapies for Glioblastoma multiforme (GBM) focus on eradicating primary tumors using radiotherapy, chemotherapy and surgical resection, but have limited success in controlling the invasive spread of glioma cells into a healthy brain, the major factor driving short survival times for patients post-diagnosis. [...] Read more.
Current therapies for Glioblastoma multiforme (GBM) focus on eradicating primary tumors using radiotherapy, chemotherapy and surgical resection, but have limited success in controlling the invasive spread of glioma cells into a healthy brain, the major factor driving short survival times for patients post-diagnosis. Transcriptomic analyses of GBM biopsies reveal clusters of membrane signaling proteins that in combination serve as robust prognostic indicators, including aquaporins and ion channels, which are upregulated in GBM and implicated in enhanced glioblastoma motility. Accumulating evidence supports our proposal that the concurrent pharmacological targeting of selected subclasses of aquaporins and ion channels could impede glioblastoma invasiveness by impairing key cellular motility pathways. Optimal sets of channels to be selected as targets for combined therapies could be tailored to the GBM cancer subtype, taking advantage of differences in patterns of expression between channels that are characteristic of GBM subtypes, as well as distinguishing them from non-cancerous brain cells such as neurons and glia. Focusing agents on a unique channel fingerprint in GBM would further allow combined agents to be administered at near threshold doses, potentially reducing off-target toxicity. Adjunct therapies which confine GBM tumors to their primary sites during clinical treatments would offer profound advantages for treatment efficacy. Full article
(This article belongs to the Special Issue The Emerging Role of Ion Channels in Brain Cancer: Mechanisms of Action and Therapeutic Targets)
►▼ Show Figures

Figure 1

44 pages, 1995 KiB  
Review
Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities
by Himani Pandey, Daryl W. T. Tang, Sunny H. Wong and Devi Lal
Cancers 2023, 15(3), 866; https://doi.org/10.3390/cancers15030866 - 30 Jan 2023
Cited by 79 | Viewed by 11404
Abstract
Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths worldwide. While CRC is thought to be an interplay between genetic and environmental factors, several lines of evidence suggest the involvement of gut microbiota in promoting inflammation and tumor progression. Gut microbiota refer [...] Read more.
Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths worldwide. While CRC is thought to be an interplay between genetic and environmental factors, several lines of evidence suggest the involvement of gut microbiota in promoting inflammation and tumor progression. Gut microbiota refer to the ~40 trillion microorganisms that inhabit the human gut. Advances in next-generation sequencing technologies and metagenomics have provided new insights into the gut microbial ecology and have helped in linking gut microbiota to CRC. Many studies carried out in humans and animal models have emphasized the role of certain gut bacteria, such as Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, in the onset and progression of CRC. Metagenomic studies have opened up new avenues for the application of gut microbiota in the diagnosis, prevention, and treatment of CRC. This review article summarizes the role of gut microbiota in CRC development and its use as a biomarker to predict the disease and its potential therapeutic applications. Full article
►▼ Show Figures

Figure 1

13 pages, 1181 KiB  
Review
CAR-T Cell Therapy and the Gut Microbiota
by Sahana Asokan, Nyssa Cullin, Christoph K. Stein-Thoeringer and Eran Elinav
Cancers 2023, 15(3), 794; https://doi.org/10.3390/cancers15030794 - 28 Jan 2023
Cited by 19 | Viewed by 7708
Abstract
Chimeric antigen receptor (CAR) - T cell cancer therapy has yielded promising results in treating hematologic malignancies in clinical studies, and a growing number of CAR-T regimens are approved for clinical usage. While the therapy is considered of great potential in expanding the [...] Read more.
Chimeric antigen receptor (CAR) - T cell cancer therapy has yielded promising results in treating hematologic malignancies in clinical studies, and a growing number of CAR-T regimens are approved for clinical usage. While the therapy is considered of great potential in expanding the cancer immunotherapy arsenal, more than half of patients receiving CAR-T infusions do not respond, while others develop significant adverse effects, collectively indicating a need for optimization of CAR-T treatment to the individual. The microbiota is increasingly suggested as a major modulator of immunotherapy responsiveness. Studying causal microbiota roles possibly contributing to CAR-T therapy efficacy, adverse effects reduction, and prediction of patient responsiveness constitutes an exciting area of active research. Herein, we discuss the latest developments implicating human microbiota involvement in CAR-T therapy, while highlighting challenges and promises in harnessing the microbiota as a predictor and modifier of CAR-T treatment towards optimized efficacy and minimization of treatment-related adverse effects. Full article
(This article belongs to the Special Issue CAR T-cell Therapy for Lymphoma Research)
►▼ Show Figures

Graphical abstract

29 pages, 1727 KiB  
Review
Current Status and Future Prospects for Esophageal Cancer
by Mahdi Sheikh, Gholamreza Roshandel, Valerie McCormack and Reza Malekzadeh
Cancers 2023, 15(3), 765; https://doi.org/10.3390/cancers15030765 - 26 Jan 2023
Cited by 140 | Viewed by 14686
Abstract
Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological subtypes with distinct epidemiological and clinical features. While the global incidence [...] Read more.
Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological subtypes with distinct epidemiological and clinical features. While the global incidence of ESCC is declining, the incidence of EAC is increasing in many countries. Decades of epidemiologic research have identified distinct environmental exposures for ESCC and EAC subtypes. Recent advances in understanding the genomic aspects of EC have advanced our understanding of EC causes and led to using specific genomic alterations in EC tumors as biomarkers for early diagnosis, treatment, and prognosis of this cancer. Nevertheless, the prognosis of EC is still poor, with a five-year survival rate of less than 20%. Currently, there are significant challenges for early detection and secondary prevention for both ESCC and EAC subtypes, but Cytosponge™ is shifting this position for EAC. Primary prevention remains the preferred strategy for reducing the global burden of EC. In this review, we will summarize recent advances, current status, and future prospects of the studies related to epidemiology, time trends, environmental risk factors, prevention, early diagnosis, and treatment for both EC subtypes. Full article
(This article belongs to the Special Issue Current Status and Future Prospects for Oesophageal Cancer)
►▼ Show Figures

Figure 1

15 pages, 787 KiB  
Review
Tumor Infiltrating Lymphocytes across Breast Cancer Subtypes: Current Issues for Biomarker Assessment
by Carmine Valenza, Beatrice Taurelli Salimbeni, Celeste Santoro, Dario Trapani, Gabriele Antonarelli and Giuseppe Curigliano
Cancers 2023, 15(3), 767; https://doi.org/10.3390/cancers15030767 - 26 Jan 2023
Cited by 43 | Viewed by 5287
Abstract
Tumor-infiltrating lymphocytes (TILs) represent a surrogate biomarker of anti-tumor, lymphocyte-mediated immunity. In early, triple-negative breast cancer, TILs have level 1B of evidence to predict clinical outcomes. TILs represent a promising biomarker to select patients who can experience a better prognosis with de-intensified cancer [...] Read more.
Tumor-infiltrating lymphocytes (TILs) represent a surrogate biomarker of anti-tumor, lymphocyte-mediated immunity. In early, triple-negative breast cancer, TILs have level 1B of evidence to predict clinical outcomes. TILs represent a promising biomarker to select patients who can experience a better prognosis with de-intensified cancer treatments and derive larger benefits from immune checkpoint inhibitors. However, the assessment and the validation of TILs as a biomarker require a prospective and rigorous demonstration of its clinical validity and utility, provided reproducible analytical performance. With pending data about the prospective validation of TILs’ clinical validity to modulate treatments in early breast cancer, this review summarizes the most important current issues and future challenges related to the implementation of TILs assessments across all breast cancer subtypes and their potential integration into clinical practice. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Focus on Multidisciplinary Approaches and Predictive Biomarkers)
►▼ Show Figures

Figure 1

31 pages, 974 KiB  
Review
Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy
by Marianna Sirico, Alberto D’Angelo, Caterina Gianni, Chiara Casadei, Filippo Merloni and Ugo De Giorgi
Cancers 2023, 15(3), 703; https://doi.org/10.3390/cancers15030703 - 23 Jan 2023
Cited by 61 | Viewed by 6801
Abstract
The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most [...] Read more.
The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice. Full article
(This article belongs to the Special Issue PI3K Pathway in Cancer)
►▼ Show Figures

Figure 1

25 pages, 1287 KiB  
Review
Treatment Strategies for Non-Small Cell Lung Cancer with Common EGFR Mutations: A Review of the History of EGFR TKIs Approval and Emerging Data
by Julian A. Marin-Acevedo, Bruna Pellini, ErinMarie O. Kimbrough, J. Kevin Hicks and Alberto Chiappori
Cancers 2023, 15(3), 629; https://doi.org/10.3390/cancers15030629 - 19 Jan 2023
Cited by 25 | Viewed by 9166
Abstract
The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC [...] Read more.
The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC in the first-line setting, therapy selection after progression on EGFR TKIs remains complex. Multiple groups are investigating novel therapies and drug combinations to determine the optimal therapy and treatment sequence for these patients. In this review, we summarize the landmark trials and history of the approval of EGFR TKIs, their efficacy and tolerability, and the role of these therapies in patients with central nervous system metastasis. We also briefly discuss the mechanisms of resistance to EGFR TKIs, ongoing attempts to overcome resistance and improve outcomes, and finalize by offering treatment sequencing recommendations. Full article
(This article belongs to the Special Issue Lung Cancer - Molecular Insights and Targeted Therapies)
►▼ Show Figures

Figure 1

22 pages, 2233 KiB  
Review
MicroRNAs in the Pathogenesis, Prognostication and Prediction of Treatment Resistance in Soft Tissue Sarcomas
by Andrea York Tiang Teo, Vivian Yujing Lim and Valerie Shiwen Yang
Cancers 2023, 15(3), 577; https://doi.org/10.3390/cancers15030577 - 18 Jan 2023
Cited by 8 | Viewed by 6204
Abstract
Soft tissue sarcomas are highly aggressive malignant neoplasms of mesenchymal origin, accounting for less than 1% of adult cancers, but comprising over 20% of paediatric solid tumours. In locally advanced, unresectable, or metastatic disease, outcomes from even the first line of systemic treatment [...] Read more.
Soft tissue sarcomas are highly aggressive malignant neoplasms of mesenchymal origin, accounting for less than 1% of adult cancers, but comprising over 20% of paediatric solid tumours. In locally advanced, unresectable, or metastatic disease, outcomes from even the first line of systemic treatment are invariably poor. MicroRNAs (miRNAs), which are short non-coding RNA molecules, target and modulate multiple dysregulated target genes and/or signalling pathways within cancer cells. Accordingly, miRNAs demonstrate great promise for their utility in diagnosing, prognosticating and improving treatment for soft tissue sarcomas. This review aims to provide an updated discussion on the known roles of specific miRNAs in the pathogenesis of sarcomas, and their potential use in prognosticating outcomes and prediction of therapeutic resistance. Full article
(This article belongs to the Topic Soft Tissue Sarcomas: Treatment and Management)
►▼ Show Figures

Figure 1

19 pages, 1305 KiB  
Review
Mass Spectrometry-Based Proteomics Workflows in Cancer Research: The Relevance of Choosing the Right Steps
by Paula Carrillo-Rodriguez, Frode Selheim and Maria Hernandez-Valladares
Cancers 2023, 15(2), 555; https://doi.org/10.3390/cancers15020555 - 16 Jan 2023
Cited by 19 | Viewed by 11349
Abstract
The qualitative and quantitative evaluation of proteome changes that condition cancer development can be achieved with liquid chromatography–mass spectrometry (LC-MS). LC-MS-based proteomics strategies are carried out according to predesigned workflows that comprise several steps such as sample selection, sample processing including labeling, MS [...] Read more.
The qualitative and quantitative evaluation of proteome changes that condition cancer development can be achieved with liquid chromatography–mass spectrometry (LC-MS). LC-MS-based proteomics strategies are carried out according to predesigned workflows that comprise several steps such as sample selection, sample processing including labeling, MS acquisition methods, statistical treatment, and bioinformatics to understand the biological meaning of the findings and set predictive classifiers. As the choice of best options might not be straightforward, we herein review and assess past and current proteomics approaches for the discovery of new cancer biomarkers. Moreover, we review major bioinformatics tools for interpreting and visualizing proteomics results and suggest the most popular machine learning techniques for the selection of predictive biomarkers. Finally, we consider the approximation of proteomics strategies for clinical diagnosis and prognosis by discussing current barriers and proposals to circumvent them. Full article
(This article belongs to the Special Issue Application of Proteomics in Cancers)
►▼ Show Figures

Graphical abstract

18 pages, 1714 KiB  
Review
Mechanisms of Acquired Resistance and Tolerance to EGFR Targeted Therapy in Non-Small Cell Lung Cancer
by Houssein Chhouri, David Alexandre and Luca Grumolato
Cancers 2023, 15(2), 504; https://doi.org/10.3390/cancers15020504 - 13 Jan 2023
Cited by 54 | Viewed by 11450
Abstract
Non-small cell lung cancers (NSCLC) harboring activating mutations of the epidermal growth factor receptor (EGFR) are treated with specific tyrosine kinase inhibitors (EGFR-TKIs) of this receptor, resulting in clinically responses that can generally last several months. Unfortunately, EGFR-targeted therapy also favors the emergence [...] Read more.
Non-small cell lung cancers (NSCLC) harboring activating mutations of the epidermal growth factor receptor (EGFR) are treated with specific tyrosine kinase inhibitors (EGFR-TKIs) of this receptor, resulting in clinically responses that can generally last several months. Unfortunately, EGFR-targeted therapy also favors the emergence of drug tolerant or resistant cells, ultimately resulting in tumor relapse. Recently, cellular barcoding strategies have arisen as a powerful tool to investigate the clonal evolution of these subpopulations in response to anti-cancer drugs. In this review, we provide an overview of the currently available treatment options for NSCLC, focusing on EGFR targeted therapy, and discuss the common mechanisms of resistance to EGFR-TKIs. We also review the characteristics of drug-tolerant persister (DTP) cells and the mechanistic basis of drug tolerance in EGFR-mutant NSCLC. Lastly, we address how cellular barcoding can be applied to investigate the response and the behavior of DTP cells upon EGFR-TKI treatment. Full article
(This article belongs to the Special Issue Mechanisms of Acquired Resistance to Targeted Therapy)
►▼ Show Figures

Figure 1

21 pages, 1058 KiB  
Review
Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management
by Sukanya Pati, Wadeed Irfan, Ahmad Jameel, Shahid Ahmed and Rabia K. Shahid
Cancers 2023, 15(2), 485; https://doi.org/10.3390/cancers15020485 - 12 Jan 2023
Cited by 364 | Viewed by 26370
Abstract
Background: Obesity or excess body fat is a major global health challenge that has not only been associated with diabetes mellitus and cardiovascular disease but is also a major risk factor for the development of and mortality related to a subgroup of cancer. [...] Read more.
Background: Obesity or excess body fat is a major global health challenge that has not only been associated with diabetes mellitus and cardiovascular disease but is also a major risk factor for the development of and mortality related to a subgroup of cancer. This review focuses on epidemiology, the relationship between obesity and the risk associated with the development and recurrence of cancer and the management of obesity. Methods: A literature search using PubMed and Google Scholar was performed and the keywords ‘obesity’ and cancer’ were used. The search was limited to research papers published in English prior to September 2022 and focused on studies that investigated epidemiology, the pathogenesis of cancer, cancer incidence and the risk of recurrence, and the management of obesity. Results: About 4–8% of all cancers are attributed to obesity. Obesity is a risk factor for several major cancers, including post-menopausal breast, colorectal, endometrial, kidney, esophageal, pancreatic, liver, and gallbladder cancer. Excess body fat results in an approximately 17% increased risk of cancer-specific mortality. The relationship between obesity and the risk associated with the development of cancer and its recurrence is not fully understood and involves altered fatty acid metabolism, extracellular matrix remodeling, the secretion of adipokines and anabolic and sex hormones, immune dysregulation, and chronic inflammation. Obesity may also increase treatment-related adverse effects and influence treatment decisions regarding specific types of cancer therapy. Structured exercise in combination with dietary support and behavior therapy are effective interventions. Treatment with glucagon-like peptide-1 analogues and bariatric surgery result in more rapid weight loss and can be considered in selected cancer survivors. Conclusions: Obesity increases cancer risk and mortality. Weight-reducing strategies in obesity-associated cancers are important interventions as a key component of cancer care. Future studies are warranted to further elucidate the complex relationship between obesity and cancer with the identification of targets for effective interventions. Full article
(This article belongs to the Special Issue Environmental Carcinogenesis)
►▼ Show Figures

Figure 1

13 pages, 521 KiB  
Review
Metastatic Prostate Cancer—A Review of Current Treatment Options and Promising New Approaches
by Philip Posdzich, Christopher Darr, Thomas Hilser, Milan Wahl, Ken Herrmann, Boris Hadaschik and Viktor Grünwald
Cancers 2023, 15(2), 461; https://doi.org/10.3390/cancers15020461 - 11 Jan 2023
Cited by 83 | Viewed by 10209
Abstract
Androgen deprivation therapy (ADT) alone has been the standard of care for many years in men with metastatic prostate cancer. Due to the limited survival under this monotherapy, many new treatment options have been developed in the last few years. Regarding hormone-sensitive prostate [...] Read more.
Androgen deprivation therapy (ADT) alone has been the standard of care for many years in men with metastatic prostate cancer. Due to the limited survival under this monotherapy, many new treatment options have been developed in the last few years. Regarding hormone-sensitive prostate cancer, combination therapies of two or three agents of ADT, androgen receptor signaling inhibitors (ARSI) and chemotherapy have been established and led to a significant benefit in overall survival. Additionally, in patients with metastatic castration-resistant prostate cancer, there are many new therapeutic approaches. Chemotherapy alone has been the standard of care in this situation. In the last years, some new therapeutic options have been developed, which led to an improved survival after progression under chemotherapy. These therapies include ARSI, PARP inhibitors and Lu-PSMA radioligand therapy. The use of a bispecific T-cell engager (BiTE) in this setting is a new promising therapeutic approach, which has not been established as standard of care yet. The role of immunotherapy in prostate cancer is still under investigation. Overall, many new treatment options make prostate cancer therapy a challenging and promising field. Full article
(This article belongs to the Special Issue Novel Therapeutics for Genitourinary Tumors)
►▼ Show Figures

Figure 1

44 pages, 1344 KiB  
Review
DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities
by María Ovejero-Sánchez, Rogelio González-Sarmiento and Ana Belén Herrero
Cancers 2023, 15(2), 448; https://doi.org/10.3390/cancers15020448 - 10 Jan 2023
Cited by 16 | Viewed by 6184
Abstract
The DNA damage response (DDR), a set of signaling pathways for DNA damage detection and repair, maintains genomic stability when cells are exposed to endogenous or exogenous DNA-damaging agents. Alterations in these pathways are strongly associated with cancer development, including ovarian cancer (OC), [...] Read more.
The DNA damage response (DDR), a set of signaling pathways for DNA damage detection and repair, maintains genomic stability when cells are exposed to endogenous or exogenous DNA-damaging agents. Alterations in these pathways are strongly associated with cancer development, including ovarian cancer (OC), the most lethal gynecologic malignancy. In OC, failures in the DDR have been related not only to the onset but also to progression and chemoresistance. It is known that approximately half of the most frequent subtype, high-grade serous carcinoma (HGSC), exhibit defects in DNA double-strand break (DSB) repair by homologous recombination (HR), and current evidence indicates that probably all HGSCs harbor a defect in at least one DDR pathway. These defects are not restricted to HGSCs; mutations in ARID1A, which are present in 30% of endometrioid OCs and 50% of clear cell (CC) carcinomas, have also been found to confer deficiencies in DNA repair. Moreover, DDR alterations have been described in a variable percentage of the different OC subtypes. Here, we overview the main DNA repair pathways involved in the maintenance of genome stability and their deregulation in OC. We also recapitulate the preclinical and clinical data supporting the potential of targeting the DDR to fight the disease. Full article
(This article belongs to the Special Issue Innovations in Diagnosis, Prognostic Evaluation, and Therapeutic Management of Gynecologic Tumors)
►▼ Show Figures

Graphical abstract

25 pages, 1780 KiB  
Review
The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited
by Kevin Dzobo, Dimakatso A. Senthebane and Collet Dandara
Cancers 2023, 15(2), 376; https://doi.org/10.3390/cancers15020376 - 6 Jan 2023
Cited by 87 | Viewed by 12777
Abstract
Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis, [...] Read more.
Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis, and highlight various ways through which tumor cells reprogram normal cells into phenotypes that are pro-tumorigenic, including cancer associated- fibroblasts, -macrophages and -endothelial cells. Tumor cells secrete numerous factors leading to the transformation of a previously anti-tumorigenic environment into a pro-tumorigenic environment. Once formed, solid tumors continue to interact with various stromal cells, including local and infiltrating fibroblasts, macrophages, mesenchymal stem cells, endothelial cells, pericytes, and secreted factors and the ECM within the tumor microenvironment (TME). The TME is key to tumorigenesis, drug response and treatment outcome. Importantly, stromal cells and secreted factors can initially be anti-tumorigenic, but over time promote tumorigenesis and induce therapy resistance. To counter hypoxia, increased angiogenesis leads to the formation of new vascular networks in order to actively promote and sustain tumor growth via the supply of oxygen and nutrients, whilst removing metabolic waste. Angiogenic vascular network formation aid in tumor cell metastatic dissemination. Successful tumor treatment and novel drug development require the identification and therapeutic targeting of pro-tumorigenic components of the TME including cancer-associated- fibroblasts (CAFs) and -macrophages (CAMs), hypoxia, blocking ECM-receptor interactions, in addition to the targeting of tumor cells. The reprogramming of stromal cells and the immune response to be anti-tumorigenic is key to therapeutic success. Lastly, this review highlights potential TME- and hypoxia-centered therapies under investigation. Full article
(This article belongs to the Special Issue Concepts to Improve Targeted Radionuclide Therapy in Cancer: Ligand Design Optimization and Application of Emerging Radionuclides and Combination Therapies)
►▼ Show Figures

Graphical abstract

25 pages, 7771 KiB  
Review
Risk Assessment and Pancreatic Cancer: Diagnostic Management and Artificial Intelligence
by Vincenza Granata, Roberta Fusco, Sergio Venanzio Setola, Roberta Galdiero, Nicola Maggialetti, Lucrezia Silvestro, Mario De Bellis, Elena Di Girolamo, Giulia Grazzini, Giuditta Chiti, Maria Chiara Brunese, Andrea Belli, Renato Patrone, Raffaele Palaia, Antonio Avallone, Antonella Petrillo and Francesco Izzo
Cancers 2023, 15(2), 351; https://doi.org/10.3390/cancers15020351 - 5 Jan 2023
Cited by 16 | Viewed by 4694
Abstract
Pancreatic cancer (PC) is one of the deadliest cancers, and it is responsible for a number of deaths almost equal to its incidence. The high mortality rate is correlated with several explanations; the main one is the late disease stage at which the [...] Read more.
Pancreatic cancer (PC) is one of the deadliest cancers, and it is responsible for a number of deaths almost equal to its incidence. The high mortality rate is correlated with several explanations; the main one is the late disease stage at which the majority of patients are diagnosed. Since surgical resection has been recognised as the only curative treatment, a PC diagnosis at the initial stage is believed the main tool to improve survival. Therefore, patient stratification according to familial and genetic risk and the creation of screening protocol by using minimally invasive diagnostic tools would be appropriate. Pancreatic cystic neoplasms (PCNs) are subsets of lesions which deserve special management to avoid overtreatment. The current PC screening programs are based on the annual employment of magnetic resonance imaging with cholangiopancreatography sequences (MR/MRCP) and/or endoscopic ultrasonography (EUS). For patients unfit for MRI, computed tomography (CT) could be proposed, although CT results in lower detection rates, compared to MRI, for small lesions. The actual major limit is the incapacity to detect and characterize the pancreatic intraepithelial neoplasia (PanIN) by EUS and MR/MRCP. The possibility of utilizing artificial intelligence models to evaluate higher-risk patients could favour the diagnosis of these entities, although more data are needed to support the real utility of these applications in the field of screening. For these motives, it would be appropriate to realize screening programs in research settings. Full article
(This article belongs to the Special Issue Diagnostics and Therapeutics Advances in Pancreatic Cancer)
►▼ Show Figures

Figure 1

28 pages, 1054 KiB  
Review
Immunotherapy for Triple-Negative Breast Cancer: Combination Strategies to Improve Outcome
by Liying Li, Fan Zhang, Zhenyu Liu and Zhimin Fan
Cancers 2023, 15(1), 321; https://doi.org/10.3390/cancers15010321 - 3 Jan 2023
Cited by 69 | Viewed by 10384
Abstract
Due to the absence of hormone receptor (both estrogen receptors and progesterone receptors) along with human epidermal growth factor receptor 2 (HER-2) amplification, the treatment of triple-negative breast cancer (TNBC) cannot benefit from endocrine or anti-HER-2 therapy. For a long time, [...] Read more.
Due to the absence of hormone receptor (both estrogen receptors and progesterone receptors) along with human epidermal growth factor receptor 2 (HER-2) amplification, the treatment of triple-negative breast cancer (TNBC) cannot benefit from endocrine or anti-HER-2 therapy. For a long time, chemotherapy was the only systemic treatment for TNBC. Due to the lack of effective treatment options, the prognosis for TNBC is extremely poor. The successful application of immune checkpoint inhibitors (ICIs) launched the era of immunotherapy in TNBC. However, the current findings show modest efficacy of programmed cell death- (ligand) 1 (PD-(L)1) inhibitors monotherapy and only a small proportion of patients can benefit from this approach. Based on the basic principles of immunotherapy and the characteristics of the tumor immune microenvironment (TIME) in TNBC, immune combination therapy is expected to further enhance the efficacy and expand the beneficiary population of patients. Given the diversity of drugs that can be combined, it is important to select effective biomarkers to identify the target population. Moreover, the side effects associated with the combination of multiple drugs should also be considered. Full article
(This article belongs to the Special Issue Immunotherapy of Triple-Negative Breast Cancer)
►▼ Show Figures

Figure 1

25 pages, 3043 KiB  
Review
Physical Exercise and the Hallmarks of Breast Cancer: A Narrative Review
by Celia García-Chico, Susana López-Ortiz, Saúl Peñín-Grandes, José Pinto-Fraga, Pedro L. Valenzuela, Enzo Emanuele, Claudia Ceci, Grazia Graziani, Carmen Fiuza-Luces, Simone Lista, Alejandro Lucia and Alejandro Santos-Lozano
Cancers 2023, 15(1), 324; https://doi.org/10.3390/cancers15010324 - 3 Jan 2023
Cited by 28 | Viewed by 11626
Abstract
Growing evidence suggests that, among the different molecular/cellular pathophysiological mechanisms associated with cancer, there are 14 hallmarks that play a major role, including: (i) sustaining proliferative signaling, (ii) evading growth suppressors, (iii) activating invasion and metastasis, (iv) enabling replicative immortality, (v) inducing angiogenesis, [...] Read more.
Growing evidence suggests that, among the different molecular/cellular pathophysiological mechanisms associated with cancer, there are 14 hallmarks that play a major role, including: (i) sustaining proliferative signaling, (ii) evading growth suppressors, (iii) activating invasion and metastasis, (iv) enabling replicative immortality, (v) inducing angiogenesis, (vi) resisting cell death, (vii) reprogramming energy metabolism, (viii) evading immune destruction, (ix) genome instability and mutations, (x) tumor-promoting inflammation, (xi) unlocking phenotypic plasticity, (xii) nonmutational epigenetic reprogramming, (xiii) polymorphic microbiomes, and (xiv) senescent cells. These hallmarks are also associated with the development of breast cancer, which represents the most prevalent tumor type in the world. The present narrative review aims to describe, for the first time, the effects of physical activity/exercise on these hallmarks. In summary, an active lifestyle, and particularly regular physical exercise, provides beneficial effects on all major hallmarks associated with breast cancer, and might therefore help to counteract the progression of the disease or its associated burden. Full article
(This article belongs to the Special Issue Breast Cancer: Tailored Rehabilitation Strategies to Address the Challenge of Survivorship Issues)
►▼ Show Figures

Figure 1

18 pages, 13914 KiB  
Review
Emerging Indications for Interventional Oncology: Expert Discussion on New Locoregional Treatments
by Roberto Iezzi, Afshin Gangi, Alessandro Posa, Uei Pua, Ping Liang, Ernesto Santos, Anil N. Kurup, Alessandro Tanzilli, Lorenzo Tenore, Davide De Leoni, Dimitrios Filippiadis, Felice Giuliante, Vincenzo Valentini, Antonio Gasbarrini, Shraga N. Goldberg, Martijn Meijerink, Riccardo Manfredi, Alexis Kelekis, Cesare Colosimo and David C. Madoff
Cancers 2023, 15(1), 308; https://doi.org/10.3390/cancers15010308 - 2 Jan 2023
Cited by 7 | Viewed by 5477
Abstract
Interventional oncology (IO) employs image-guided techniques to perform minimally invasive procedures, providing lower-risk alternatives to many traditional medical and surgical therapies for cancer patients. Since its advent, due to rapidly evolving research development, its role has expanded to encompass the diagnosis and treatment [...] Read more.
Interventional oncology (IO) employs image-guided techniques to perform minimally invasive procedures, providing lower-risk alternatives to many traditional medical and surgical therapies for cancer patients. Since its advent, due to rapidly evolving research development, its role has expanded to encompass the diagnosis and treatment of diseases across multiple body systems. In detail, interventional oncology is expanding its role across a wide spectrum of disease sites, offering a potential cure, control, or palliative care for many types of cancer patients. Due to its widespread use, a comprehensive review of the new indications for locoregional procedures is mandatory. This article summarizes the expert discussion and report from the “MIOLive Meet SIO” (Society of Interventional Oncology) session during the last MIOLive 2022 (Mediterranean Interventional Oncology Live) congress held in Rome, Italy, integrating evidence-reported literature and experience-based perceptions. The aim of this paper is to provide an updated review of the new techniques and devices available for innovative indications not only to residents and fellows but also to colleagues approaching locoregional treatments. Full article
►▼ Show Figures

Figure 1

20 pages, 1149 KiB  
Review
Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma
by Valentina Evdokimova, Hendrik Gassmann, Laszlo Radvanyi and Stefan E. G. Burdach
Cancers 2023, 15(1), 272; https://doi.org/10.3390/cancers15010272 - 30 Dec 2022
Cited by 33 | Viewed by 5089
Abstract
We argue here that in many ways, Ewing sarcoma (EwS) is a unique tumor entity and yet, it shares many commonalities with other immunologically cold solid malignancies. From the historical perspective, EwS, osteosarcoma (OS) and other bone and soft-tissue sarcomas were the first [...] Read more.
We argue here that in many ways, Ewing sarcoma (EwS) is a unique tumor entity and yet, it shares many commonalities with other immunologically cold solid malignancies. From the historical perspective, EwS, osteosarcoma (OS) and other bone and soft-tissue sarcomas were the first types of tumors treated with the immunotherapy approach: more than 100 years ago American surgeon William B. Coley injected his patients with a mixture of heat-inactivated bacteria, achieving survival rates apparently higher than with surgery alone. In contrast to OS which exhibits recurrent somatic copy-number alterations, EwS possesses one of the lowest mutation rates among cancers, being driven by a single oncogenic fusion protein, most frequently EWS-FLI1. In spite these differences, both EwS and OS are allied with immune tolerance and low immunogenicity. We discuss here the potential mechanisms of immune escape in these tumors, including low representation of tumor-specific antigens, low expression levels of MHC-I antigen-presenting molecules, accumulation of immunosuppressive M2 macrophages and myeloid proinflammatory cells, and release of extracellular vesicles (EVs) which are capable of reprogramming host cells in the tumor microenvironment and systemic circulation. We also discuss the vulnerabilities of EwS and OS and potential novel strategies for their targeting. Full article
(This article belongs to the Special Issue Ewing Sarcoma: Basic Biology, Clinical Challenges and Future Perspectives)
►▼ Show Figures

Figure 1

14 pages, 1645 KiB  
Review
Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors
by Alessandra Dimino, Chiara Brando, Laura Algeri, Valerio Gristina, Erika Pedone, Marta Peri, Alessandro Perez, Ida De Luca, Roberta Sciacchitano, Luigi Magrin, Tancredi Didier Bazan Russo, Marco Bono, Nadia Barraco, Silvia Contino, Maria La Mantia, Antonio Galvano, Giuseppe Badalamenti, Antonio Russo, Viviana Bazan and Lorena Incorvaia
Cancers 2023, 15(1), 216; https://doi.org/10.3390/cancers15010216 - 29 Dec 2022
Cited by 9 | Viewed by 2412
Abstract
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies [...] Read more.
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlighted the relevance of the TME in GISTs, with possible implications for clinical practice in the near future. Moreover, the expression of immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and their relationship to the clinical phenotype in GIST are emerging as potential prognostic biomarkers. Looking forward, these variables related to the underlying tumoral microenvironment in GIST, though limited to still-ongoing trials, might lead to the potential use of immunotherapy, alone or in combination with targeted therapy, in advanced TKI-refractory GISTs. This review aims to deepen understanding of the potential link between mutational status and the immune microenvironment in GIST. Full article
(This article belongs to the Special Issue Gastrointestinal Stromal Tumors (GIST): Opportunity and Challenges in Diagnosis and Treatment)
►▼ Show Figures

Figure 1

27 pages, 1386 KiB  
Review
CAR-NK as a Rapidly Developed and Efficient Immunotherapeutic Strategy against Cancer
by Marta Włodarczyk and Beata Pyrzynska
Cancers 2023, 15(1), 117; https://doi.org/10.3390/cancers15010117 - 24 Dec 2022
Cited by 27 | Viewed by 10847
Abstract
Chimeric antigen receptor (CAR)-modified T cell therapy has been rapidly developing in recent years, ultimately revolutionizing immunotherapeutic strategies and providing significant anti-tumor potency, mainly in treating hematological neoplasms. However, graft-versus-host disease (GVHD) and other adverse effects, such as cytokine release syndromes (CRS) and [...] Read more.
Chimeric antigen receptor (CAR)-modified T cell therapy has been rapidly developing in recent years, ultimately revolutionizing immunotherapeutic strategies and providing significant anti-tumor potency, mainly in treating hematological neoplasms. However, graft-versus-host disease (GVHD) and other adverse effects, such as cytokine release syndromes (CRS) and neurotoxicity associated with CAR-T cell infusion, have raised some concerns about the broad application of this therapy. Natural killer (NK) cells have been identified as promising alternative platforms for CAR-based therapies because of their unique features, such as a lack of human leukocyte antigen (HLA)-matching restriction, superior safety, and better anti-tumor activity when compared with CAR-T cells. The lack of CRS, neurotoxicity, or GVHD, in the case of CAR-NK therapy, in addition to the possibility of using allogeneic NK cells as a CAR platform for “off-the-shelf” therapy, opens new windows for strategic opportunities. This review underlines recent design achievements in CAR constructs and summarizes preclinical studies’ results regarding CAR-NK therapies’ safety and anti-tumor potency. Additionally, new approaches in CAR-NK technology are briefly described, and currently registered clinical trials are listed. Full article
(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)
►▼ Show Figures

Figure 1

19 pages, 801 KiB  
Review
Role of Machine Learning in Precision Oncology: Applications in Gastrointestinal Cancers
by Azadeh Tabari, Shin Mei Chan, Omar Mustafa Fathy Omar, Shams I. Iqbal, Michael S. Gee and Dania Daye
Cancers 2023, 15(1), 63; https://doi.org/10.3390/cancers15010063 - 22 Dec 2022
Cited by 24 | Viewed by 6817
Abstract
Gastrointestinal (GI) cancers, consisting of a wide spectrum of pathologies, have become a prominent health issue globally. Despite medical imaging playing a crucial role in the clinical workflow of cancers, standard evaluation of different imaging modalities may provide limited information. Accurate tumor detection, [...] Read more.
Gastrointestinal (GI) cancers, consisting of a wide spectrum of pathologies, have become a prominent health issue globally. Despite medical imaging playing a crucial role in the clinical workflow of cancers, standard evaluation of different imaging modalities may provide limited information. Accurate tumor detection, characterization, and monitoring remain a challenge. Progress in quantitative imaging analysis techniques resulted in ”radiomics”, a promising methodical tool that helps to personalize diagnosis and treatment optimization. Radiomics, a sub-field of computer vision analysis, is a bourgeoning area of interest, especially in this era of precision medicine. In the field of oncology, radiomics has been described as a tool to aid in the diagnosis, classification, and categorization of malignancies and to predict outcomes using various endpoints. In addition, machine learning is a technique for analyzing and predicting by learning from sample data, finding patterns in it, and applying it to new data. Machine learning has been increasingly applied in this field, where it is being studied in image diagnosis. This review assesses the current landscape of radiomics and methodological processes in GI cancers (including gastric, colorectal, liver, pancreatic, neuroendocrine, GI stromal, and rectal cancers). We explain in a stepwise fashion the process from data acquisition and curation to segmentation and feature extraction. Furthermore, the applications of radiomics for diagnosis, staging, assessment of tumor prognosis and treatment response according to different GI cancer types are explored. Finally, we discussed the existing challenges and limitations of radiomics in abdominal cancers and investigate future opportunities. Full article
(This article belongs to the Special Issue Multi-Modality Imaging and Multi-Omics Approach of Cancers with Machine Learning/Deep Learning)
►▼ Show Figures

Figure 1

18 pages, 2854 KiB  
Review
Liver Microenvironment Response to Prostate Cancer Metastasis and Hormonal Therapy
by Alison K. Buxton, Salma Abbasova, Charlotte L. Bevan and Damien A. Leach
Cancers 2022, 14(24), 6189; https://doi.org/10.3390/cancers14246189 - 15 Dec 2022
Cited by 10 | Viewed by 4904
Abstract
Prostate cancer-associated deaths arise from disease progression and metastasis. Metastasis to the liver is associated with the worst clinical outcomes for prostate cancer patients, and these metastatic tumors can be particularly resistant to the currently widely used chemotherapy and hormonal therapies, such as [...] Read more.
Prostate cancer-associated deaths arise from disease progression and metastasis. Metastasis to the liver is associated with the worst clinical outcomes for prostate cancer patients, and these metastatic tumors can be particularly resistant to the currently widely used chemotherapy and hormonal therapies, such as anti-androgens which block androgen synthesis or directly target the androgen receptor. The incidence of liver metastases is reportedly increasing, with a potential correlation with use of anti-androgen therapies. A key player in prostate cancer progression and therapeutic response is the microenvironment of the tumor(s). This is a dynamic and adaptive collection of cells and proteins, which impart signals and stimuli that can alter biological processes within prostate cancer cells. Investigation in the prostate primary site has demonstrated that cells of the microenvironment are also responsive to hormones and hormonal therapies. In this review, we collate information about what happens when cancer moves to the liver: the types of prostate cancer cells that metastasize there, the response of resident mesenchymal cells of the liver, and how the interactions between the cancer cells and the microenvironment may be altered by hormonal therapy. Full article
(This article belongs to the Collection Prostate Cancer: Pathophysiology, Pathology and Therapy)
►▼ Show Figures

Figure 1

56 pages, 2099 KiB  
Review
Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?
by Mariana Tannoury, Delphine Garnier, Santos A. Susin and Brigitte Bauvois
Cancers 2022, 14(24), 6026; https://doi.org/10.3390/cancers14246026 - 7 Dec 2022
Cited by 9 | Viewed by 5882
Abstract
Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today’s commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of [...] Read more.
Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today’s commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of inhibitors of anti-apoptotic proteins from the B-cell lymphoma/leukemia 2 family and the B-cell receptor (BCR) signaling pathway. Orally administered small-molecule inhibitors of Bcl-2 protein and BCR partners (e.g., Bruton’s tyrosine kinase and phosphatidylinositol-3 kinase) have already been included (as monotherapies or combination therapies) in the standard of care for selected B cell malignancies. Agonistic monoclonal antibodies and their derivatives (antibody–drug conjugates, antibody–radioisotope conjugates, bispecific T cell engagers, and chimeric antigen receptor-modified T cells) targeting tumor-associated antigens (TAAs, such as CD19, CD20, CD22, and CD38) are indicated for treatment (as monotherapies or combination therapies) of patients with B cell tumors. However, given that some patients are either refractory to current therapies or relapse after treatment, novel therapeutic strategies are needed. Here, we review current strategies for managing B cell malignancies, with a focus on the ongoing clinical development of more effective, selective drugs targeting these molecules, as well as other TAAs and signaling proteins. The observed impact of metabolic reprogramming on B cell pathophysiology highlights the promise of targeting metabolic checkpoints in the treatment of these disorders. Full article
(This article belongs to the Section Cancer Biomarkers)
►▼ Show Figures

Figure 1

30 pages, 1375 KiB  
Review
Efficacy, Safety, and Challenges of CAR T-Cells in the Treatment of Solid Tumors
by Qiuqiang Chen, Lingeng Lu and Wenxue Ma
Cancers 2022, 14(23), 5983; https://doi.org/10.3390/cancers14235983 - 3 Dec 2022
Cited by 26 | Viewed by 6702
Abstract
Immunotherapy has been the fifth pillar of cancer treatment in the past decade. Chimeric antigen receptor (CAR) T-cell therapy is a newly designed adoptive immunotherapy that is able to target and further eliminate cancer cells by engaging with MHC-independent tumor-antigens. CAR T-cell therapy [...] Read more.
Immunotherapy has been the fifth pillar of cancer treatment in the past decade. Chimeric antigen receptor (CAR) T-cell therapy is a newly designed adoptive immunotherapy that is able to target and further eliminate cancer cells by engaging with MHC-independent tumor-antigens. CAR T-cell therapy has exhibited conspicuous clinical efficacy in hematological malignancies, but more than half of patients will relapse. Of note, the efficacy of CAR T-cell therapy has been even more disappointing in solid tumors. These challenges mainly include (1) the failures of CAR T-cells to treat highly heterogeneous solid tumors due to the difficulty in identifying unique tumor antigen targets, (2) the expression of target antigens in non-cancer cells, (3) the inability of CAR T-cells to effectively infiltrate solid tumors, (4) the short lifespan and lack of persistence of CAR T-cells, and (5) cytokine release syndrome and neurotoxicity. In combination with these characteristics, the ideal CAR T-cell therapy for solid tumors should maintain adequate T-cell response over a long term while sparing healthy tissues. This article reviewed the status, clinical application, efficacy, safety, and challenges of CAR T-cell therapies, as well as the latest progress of CAR T-cell therapies for solid tumors. In addition, the potential strategies to improve the efficacy of CAR T-cells and prevent side effects in solid tumors were also explored. Full article
(This article belongs to the Special Issue Cytokines in Clinical Cancer Immunotherapy)
►▼ Show Figures

Figure 1

9 pages, 246 KiB  
Review
Circulating Human Papillomavirus DNA in Head and Neck Squamous Cell Carcinoma: Possible Applications and Future Directions
by Dauren Adilbay, Saudamini Lele, John Pang, Ameya Asarkar, Jason Calligas and Cherie-Ann Nathan
Cancers 2022, 14(23), 5946; https://doi.org/10.3390/cancers14235946 - 1 Dec 2022
Cited by 13 | Viewed by 2938
Abstract
There has been a rising trend in HPV-induced head and neck cancers in the last several decades. This subgroup of squamous cell carcinoma is mostly located in the oropharynx and comprises a subset of patients who are typically younger and without the usual [...] Read more.
There has been a rising trend in HPV-induced head and neck cancers in the last several decades. This subgroup of squamous cell carcinoma is mostly located in the oropharynx and comprises a subset of patients who are typically younger and without the usual risk factors of smoking and alcohol use. As the prognosis of HPV-induced OPC is more favorable, there is a desire to properly select these patients for de-intensification protocols while identifying individuals who may suffer treatment failure. Here, we describe recent developments in circulating tumor HPV DNA as a marker of HPV-positive oropharyngeal cancer that can potentially be used as a diagnostic tool to stratify patients for de-escalation strategies and to survey for recurrence. Full article
(This article belongs to the Special Issue Epidemiology of HPV-Associated Oropharyngeal Squamous Cell Carcinoma)
43 pages, 2814 KiB  
Review
Physical Activity as the Best Supportive Care in Cancer: The Clinician’s and the Researcher’s Perspectives
by Cécile Torregrosa, Frédéric Chorin, Eva Ester Molina Beltran, Cindy Neuzillet and Victoire Cardot-Ruffino
Cancers 2022, 14(21), 5402; https://doi.org/10.3390/cancers14215402 - 2 Nov 2022
Cited by 26 | Viewed by 9812
Abstract
Multidisciplinary supportive care, integrating the dimensions of exercise alongside oncological treatments, is now regarded as a new paradigm to improve patient survival and quality of life. Its impact is important on the factors that control tumor development, such as the immune system, inflammation, [...] Read more.
Multidisciplinary supportive care, integrating the dimensions of exercise alongside oncological treatments, is now regarded as a new paradigm to improve patient survival and quality of life. Its impact is important on the factors that control tumor development, such as the immune system, inflammation, tissue perfusion, hypoxia, insulin resistance, metabolism, glucocorticoid levels, and cachexia. An increasing amount of research has been published in the last years on the effects of physical activity within the framework of oncology, marking the appearance of a new medical field, commonly known as “exercise oncology”. This emerging research field is trying to determine the biological mechanisms by which, aerobic exercise affects the incidence of cancer, the progression and/or the appearance of metastases. We propose an overview of the current state of the art physical exercise interventions in the management of cancer patients, including a pragmatic perspective with tips for routine practice. We then develop the emerging mechanistic views about physical exercise and their potential clinical applications. Moving toward a more personalized, integrated, patient-centered, and multidisciplinary management, by trying to understand the different interactions between the cancer and the host, as well as the impact of the disease and the treatments on the different organs, this seems to be the most promising method to improve the care of cancer patients. Full article
(This article belongs to the Special Issue Physical Activity and Cancer Care)
►▼ Show Figures

Graphical abstract

27 pages, 3015 KiB  
Review
In Vivo Models for Prostate Cancer Research
by Robert Adamiecki, Anita Hryniewicz-Jankowska, Maria A. Ortiz, Xiang Li, Baylee A. Porter-Hansen, Imad Nsouli, Gennady Bratslavsky and Leszek Kotula
Cancers 2022, 14(21), 5321; https://doi.org/10.3390/cancers14215321 - 28 Oct 2022
Cited by 8 | Viewed by 4817
Abstract
In 2022, prostate cancer (PCa) is estimated to be the most commonly diagnosed cancer in men in the United States—almost 270,000 American men are estimated to be diagnosed with PCa in 2022. This review compares and contrasts in vivo models of PCa with [...] Read more.
In 2022, prostate cancer (PCa) is estimated to be the most commonly diagnosed cancer in men in the United States—almost 270,000 American men are estimated to be diagnosed with PCa in 2022. This review compares and contrasts in vivo models of PCa with regards to the altered genes, signaling pathways, and stages of tumor progression associated with each model. The main type of model included in this review are genetically engineered mouse models, which include conditional and constitutive knockout model. 2D cell lines, 3D organoids and spheroids, xenografts and allografts, and patient derived models are also included. The major applications, advantages and disadvantages, and ease of use and cost are unique to each type of model, but they all make it easier to translate the tumor progression that is seen in the mouse prostate to the human prostate. Although both human and mouse prostates are androgen-dependent, the fact that the native, genetically unaltered prostate in mice cannot give rise to carcinoma is an especially critical component of PCa models. Thanks to the similarities between the mouse and human genome, our knowledge of PCa has been expanded, and will continue to do so, through models of PCa. Full article
(This article belongs to the Topic Animal Model in Biomedical Research, 2nd Volume)
►▼ Show Figures

Figure 1

30 pages, 1177 KiB  
Review
Dietary Interventions in Cancer Treatment and Response: A Comprehensive Review
by Benjamin D. Mercier, Eemon Tizpa, Errol J. Philip, Qianhua Feng, Ziyi Huang, Reeny M. Thomas, Sumanta K. Pal, Tanya B. Dorff and Yun R. Li
Cancers 2022, 14(20), 5149; https://doi.org/10.3390/cancers14205149 - 20 Oct 2022
Cited by 29 | Viewed by 10240
Abstract
Chemotherapy and radiotherapy are first-line treatments in the management of advanced solid tumors. Whereas these treatments are directed at eliminating cancer cells, they cause significant adverse effects that can be detrimental to a patient’s quality of life and even life-threatening. Diet is a [...] Read more.
Chemotherapy and radiotherapy are first-line treatments in the management of advanced solid tumors. Whereas these treatments are directed at eliminating cancer cells, they cause significant adverse effects that can be detrimental to a patient’s quality of life and even life-threatening. Diet is a modifiable risk factor that has been shown to affect cancer risk, recurrence, and treatment toxicity, but little information is known how diet interacts with cancer treatment modalities. Although dietary interventions, such as intermittent fasting and ketogenic diets, have shown promise in pre-clinical studies by reducing the toxicity and increasing the efficacy of chemotherapeutics, there remains a limited number of clinical studies in this space. This review surveys the impact of dietary interventions (caloric restriction, intermittent and short-term fasting, and ketogenic diet) on cancer treatment outcomes in both pre-clinical and clinical studies. Early studies support a complementary role for these dietary interventions in improving patient quality of life across multiple cancer types by reducing toxicity and perhaps a benefit in treatment efficacy. Larger, phase III, randomized clinical trials are ultimately necessary to evaluate the efficacy of these dietary interventions in improving oncologic or quality of life outcomes for patients that are undergoing chemotherapy or radiotherapy. Full article
(This article belongs to the Special Issue The Mechanisms of Physical Activity, Diet, and Body Composition in Cancer Prevention and Control)
►▼ Show Figures

Figure 1

21 pages, 2437 KiB  
Review
Chronotherapy: Circadian Rhythms and Their Influence in Cancer Therapy
by Ana Amiama-Roig, Eva M. Verdugo-Sivianes, Amancio Carnero and José-Ramón Blanco
Cancers 2022, 14(20), 5071; https://doi.org/10.3390/cancers14205071 - 17 Oct 2022
Cited by 47 | Viewed by 11601
Abstract
Living organisms present rhythmic fluctuations every 24 h in their behavior and metabolism to anticipate changes in the environment. These fluctuations are controlled by a very complex molecular mechanism, the circadian clock, that regulates the expression of multiple genes to ensure the right [...] Read more.
Living organisms present rhythmic fluctuations every 24 h in their behavior and metabolism to anticipate changes in the environment. These fluctuations are controlled by a very complex molecular mechanism, the circadian clock, that regulates the expression of multiple genes to ensure the right functioning of the body. An individual’s circadian system is altered during aging, and this is related to numerous age-associated pathologies and other alterations that could contribute to the development of cancer. Nowadays, there is an increasing interest in understanding how circadian rhythms could be used in the treatment of cancer. Chronotherapy aims to understand the impact that biological rhythms have on the response to a therapy to optimize its action, maximize health benefits and minimize possible adverse effects. Clinical trials so far have confirmed that optimal timing of treatment with chemo or immunotherapies could decrease drug toxicity and increase efficacy. Instead, chronoradiotherapy seems to minimize treatment-related symptoms rather than tumor progression or patient survival. In addition, potential therapeutic targets within the molecular clock have also been identified. Therefore, results of the application of chronotherapy in cancer therapy until now are challenging, feasible, and could be applied to clinical practice to improve cancer treatment without additional costs. However, different limitations and variables such as age, sex, or chronotypes, among others, should be overcome before chronotherapy can really be put into clinical practice. Full article
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying article 401-450 on page 9 of 18.
Back to TopTop