Journal Description
Cancers
Cancers
is a peer-reviewed, open access journal of oncology, published semimonthly online by MDPI. The Irish Association for Cancer Research (IACR), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and Spanish Group for Cancer Immuno-Biotherapy (GÉTICA) are affiliated with Cancers and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Oncology) / CiteScore - Q1 (Oncology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.9 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 18 topical sections.
- Companion journals for Cancers include: Radiation and Onco.
Impact Factor:
5.2 (2022);
5-Year Impact Factor:
5.6 (2022)
Latest Articles
Harnessing ctDNA in Advanced Melanoma: A Promising Tool for Informed Clinical Decisions
Cancers 2024, 16(6), 1197; https://doi.org/10.3390/cancers16061197 (registering DOI) - 18 Mar 2024
Abstract
Cutaneous melanoma, an aggressive malignancy, has undergone significant transformation in clinical management with the introduction of immune checkpoint inhibitors (ICIs) and targeted therapies. Current monitoring methods, such as imaging scans, present limitations, prompting exploration of alternative biomarkers. This review comprehensively explores the role
[...] Read more.
Cutaneous melanoma, an aggressive malignancy, has undergone significant transformation in clinical management with the introduction of immune checkpoint inhibitors (ICIs) and targeted therapies. Current monitoring methods, such as imaging scans, present limitations, prompting exploration of alternative biomarkers. This review comprehensively explores the role of circulating tumor DNA (ctDNA) in advanced melanoma, covering technical aspects, detection methods, and its prognostic and predictive value. Recent findings underscore ctDNA’s potential applications and implications in clinical practice. This review emphasizes the need for precise and dynamic biomarkers in melanoma care, positioning ctDNA as a promising blood-based tool for prognosis, treatment response, and resistance mechanisms. The technical nuances of ctDNA detection, association with melanoma mutations, and its role in guiding therapeutic decisions for immunotherapy and targeted therapy underscore its multifaceted utility, marking a paradigm shift in clinical decision-making and offering a promising trajectory for personalized and informed care in advanced melanoma.
Full article
(This article belongs to the Special Issue Advances in Genetic and Molecular Approaches to Skin Cancer)
Open AccessReview
Efficacy of NSCLC Rechallenge with Immune Checkpoint Inhibitors Following Disease Progression or Relapse
by
Maria Effrosyni Livanou, Vasiliki Nikolaidou, Vasileios Skouras, Oraianthi Fiste and Elias Kotteas
Cancers 2024, 16(6), 1196; https://doi.org/10.3390/cancers16061196 (registering DOI) - 18 Mar 2024
Abstract
Immune checkpoint inhibitors (ICIs) are at the forefront of advanced non-small-cell lung cancer (NSCLC) treatment. Still, only 27–46% of patients respond to initial therapy with ICIs, and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options
[...] Read more.
Immune checkpoint inhibitors (ICIs) are at the forefront of advanced non-small-cell lung cancer (NSCLC) treatment. Still, only 27–46% of patients respond to initial therapy with ICIs, and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6–3.1 months and a Disease Control Rate (DCR) of 21.4–41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75–81%, according to post hoc analyses of several clinical trials. Future research on ICI rechallenge for NSCLC should focus on better patient stratification to reflect the underlying biology of immunotherapy resistance more accurately. In this review, we summarize evidence regarding rechallenge immunotherapy efficacy following NSCLC disease progression or relapse, as well as ongoing trials on immunotherapy rechallenge.
Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
Open AccessReview
CD44 in Bladder Cancer
by
Jason Duex and Dan Theodorescu
Cancers 2024, 16(6), 1195; https://doi.org/10.3390/cancers16061195 (registering DOI) - 18 Mar 2024
Abstract
The glycoprotein CD44, with its many isoforms and variations in carbohydrate patterning, participates in a diverse set of cellular functions. This fact leads to the protein playing a role in many normal and pathologic cellular processes including a role in cancer progression and
[...] Read more.
The glycoprotein CD44, with its many isoforms and variations in carbohydrate patterning, participates in a diverse set of cellular functions. This fact leads to the protein playing a role in many normal and pathologic cellular processes including a role in cancer progression and metastasis. These same facts make CD44 a strong therapeutic target in many cancer types, including bladder cancer.
Full article
(This article belongs to the Special Issue The Biology of CD44 and Its Role in Cancer Progression: Therapeutic Implications)
Open AccessArticle
Cachexia-Affected Survival Based on Inflammatory Parameters Compared to Complex Conventional Nutritional Assessments in Patients with Pancreatic Cancer and Other Gastrointestinal Tumors—The CONKO 020 Investigation
by
Johanna W. Meyer-Knees, Janina Falkenthal, Dominik Geisel, Christopher C. M. Neumann, Georg Hilfenhaus, Lars U. Stephan, Wenzel Schöning, Thomas Malinka, Johann Pratschke, Sebastian Stintzing and Uwe Pelzer
Cancers 2024, 16(6), 1194; https://doi.org/10.3390/cancers16061194 (registering DOI) - 18 Mar 2024
Abstract
Background: Pancreatic adenocarcinoma (PDAC) is still a complex, devastating disease. Cachexia symptoms frequently impair patient survival. This accompanying syndrome is commonly diagnosed late, when clinical signs become evident. Early diagnosis using conventional measurement methods is often difficult, and the discrimination of this disease
[...] Read more.
Background: Pancreatic adenocarcinoma (PDAC) is still a complex, devastating disease. Cachexia symptoms frequently impair patient survival. This accompanying syndrome is commonly diagnosed late, when clinical signs become evident. Early diagnosis using conventional measurement methods is often difficult, and the discrimination of this disease from cancer progression is challenging and often overlaps. The aim of this study was to analyze whether conventional nutritional assessments or laboratory biomarkers are better predictive tools for the early detection of patients at risk of reduced survival. Methods: We analyzed a prospective predefined cohort of 182 patients with gastrointestinal cancer, 120 patients with PDAC and—as controls—62 patients with other gastrointestinal adenocarcinoma (oAC), from whom we have sufficient data of protocol-defined conventional nutritional assessments, clinical data, and specific laboratory parameters. Results: at the time of tumor diagnosis, high inflammatory biomarkers (c-reactive protein (CRP), interleukin-6 (IL-6)) and albumin serum levels were associated with impaired OS in PDAC patients, but not in patients with oAC. Hemoglobin, body mass index (BMI), and bioelectrical assessments alone did not have a prognostic impact at the time of diagnosis. In a multivariate analysis, only CRP (HR 1.91 (1.25–2.92), p = 0.003) was found to be an independent prognostic factor in PDAC patients. Over the course of the disease in PDAC patients, inflammatory biomarkers, albumin, hemoglobin, and bioelectrical assessments were associated with impaired OS. In multivariate testing, CRP (HR 2.21 (1.38–3.55), p < 0.001) and albumin (HR 1.71 (1.05–2.77), p = 0.030) were found to be independent prognostic factors in PDAC patients. Conclusion: Specifically for PDAC patients, high inflammatory index and albumin serum levels potentially represent a sufficient early surrogate marker to detect patients at high risk of impaired OS better than complex conventional methods. These findings could help to identify patients who may benefit from early therapeutic interventions.
Full article
(This article belongs to the Special Issue Inflammation in Cancers)
Open AccessOpinion
The Added Value of Transcatheter CT Hepatic Angiography (CTHA) Image Guidance in Percutaneous Thermal Liver Ablation: An Experts’ Opinion Pictorial Essay
by
Robbert S. Puijk, Madelon Dijkstra, Susan van der Lei, Hannah H. Schulz, Danielle J. W. Vos, Florentine E. F. Timmer, Bart Geboers, Hester J. Scheffer, Jan J. J. de Vries, Maarten L. J. Smits, Rutger C. G. Bruijnen, Frédéric Deschamps, Thierry de Baère, Bruno C. Odisio and Martijn R. Meijerink
Cancers 2024, 16(6), 1193; https://doi.org/10.3390/cancers16061193 - 18 Mar 2024
Abstract
With the rapidly evolving field of image-guided tumor ablation, there is an increasing demand and need for tools to optimize treatment success. Known factors affecting the success of (non-)thermal liver ablation procedures are the ability to optimize tumor and surrounding critical structure visualization,
[...] Read more.
With the rapidly evolving field of image-guided tumor ablation, there is an increasing demand and need for tools to optimize treatment success. Known factors affecting the success of (non-)thermal liver ablation procedures are the ability to optimize tumor and surrounding critical structure visualization, ablation applicator targeting, and ablation zone confirmation. A recent study showed superior local tumor progression-free survival and local control outcomes when using transcatheter computed tomography hepatic angiography (CTHA) guidance in percutaneous liver ablation procedures. This pictorial review provides eight clinical cases from three institutions, MD Anderson (Houston, TX, USA), Gustave Roussy (Paris, France), and Amsterdam UMC (Amsterdam, The Netherlands), with the intent to demonstrate the added value of real-time CTHA guided tumor ablation for primary liver tumors and liver-only metastatic disease. The clinical illustrations highlight the ability to improve the detectability of the initial target liver tumor(s) and identify surrounding critical vascular structures, detect ‘vanished’ and/or additional tumors intraprocedurally, differentiate local tumor progression from non-enhancing scar tissue, and promptly detect and respond to iatrogenic hemorrhagic events. Although at the cost of adding a minor but safe intervention, CTHA-guided liver tumor ablation minimizes complications of the actual ablation procedure, reduces the number of repeat ablations, and improves the oncological outcome of patients with liver malignancies. Therefore, we recommend adopting CTHA as a potential quality-improving guiding method within the (inter)national standards of practice.
Full article
(This article belongs to the Special Issue Diagnosis and Therapeutic Management of Gastrointestinal Cancers)
Open AccessArticle
Comprehensive 3DCRT Hypofractionated Radiotherapy Schedule for Localized Prostate Adenocarcinoma in the Era of IMRT: Dosimetric and Endoscopic Analysis
by
Andromachi Kougioumtzopoulou, Nick Syrigos, Anna Zygogianni, Ioannis Georgakopoulos, Kalliopi Platoni, George Patatoukas, Kimon Tzannis, Aristotelis Bamias, Nikolaos Kelekis and Vasileios Kouloulias
Cancers 2024, 16(6), 1192; https://doi.org/10.3390/cancers16061192 - 18 Mar 2024
Abstract
Background: Moderate hypofractionated radiotherapy (MHRT) has emerged as the preferred treatment modality for localized prostate cancer based on randomized controlled studies regarding efficacy and toxicity using contemporary radiotherapy techniques. In the setting of MHRT, available data on dosimetric parameters and late rectal toxicity
[...] Read more.
Background: Moderate hypofractionated radiotherapy (MHRT) has emerged as the preferred treatment modality for localized prostate cancer based on randomized controlled studies regarding efficacy and toxicity using contemporary radiotherapy techniques. In the setting of MHRT, available data on dosimetric parameters and late rectal toxicity are limited. Aim: To present the effects of MHRT on late rectal toxicity while conducting an extensive dosimetric analysis in conjunction with rectoscopy results. Methods: This is a prospective study including patients with intermediate-risk prostate adenocarcinoma. All patients were treated with MHRT 44 Gy in 16 fractions to the seminal vesicles and to the prostate, followed by a sequential boost to the prostate alone of 16.5 Gy in 6 fractions delivered with three-dimensional conformal radiation therapy (3DCRT). Acute and late toxicity were assessed. Endoscopy was performed at baseline, every 3 months post-therapy for the first year, and every 6 months for the year after. The Vienna Rectoscopy Score (VRS) was used to assess rectal mucosal injury related to radiotherapy. Dosimetric analysis for the rectum, rectal wall, and its subsegments (upper, mid, and low 1/3) was performed. Results: Between September 2015 and December 2019, 20 patients enrolled. Grade 1 late gastrointestinal toxicity occurred in 10% of the patients, whereas 5% had a grade ≥2. Twelve months post radiotherapy: 4 (20%) patients had VRS 1; 2 (10%) patients had VRS 2; 1(5%) patient had VRS 3. 24 months post radiotherapy, VRS 1 was observed in 4 patients (20%) and VRS 2 in 3 (15%) patients. The dosimetric analysis demonstrated noticeable variations between the rectum, rectal wall, and rectal wall subsegments. The dosimetric analysis of the rectum, rectal wall, and its mid and low segments with respect to rectoscopy findings showed that the higher dose endpoints V52.17Gy and V56.52Gy are associated with rectal mucosal injury. Conclusions: A thorough delineation of the rectal wall and its subsegments, together with the dosimetric analysis of these structures, may reduce late rectal toxicity. Dosimetric parameters such as V52.17Gy and V56.52Gy were identified to have a significant impact on rectal mucosal injury; additional dose endpoint validation and its relation to late GI toxicity is needed.
Full article
(This article belongs to the Special Issue Cancer-Therapy-Related Adverse Events in Organs)
►▼
Show Figures
Figure 1
Open AccessReview
Cancer Screening: Present Recommendations, the Development of Multi-Cancer Early Development Tests, and the Prospect of Universal Cancer Screening
by
Laurenția Nicoleta Galeș, Mihai-Andrei Păun, Rodica Maricela Anghel and Oana Gabriela Trifănescu
Cancers 2024, 16(6), 1191; https://doi.org/10.3390/cancers16061191 - 18 Mar 2024
Abstract
Cancer continues to pose a considerable challenge to global health. In the search for innovative strategies to combat this complex enemy, the concept of universal cancer screening has emerged as a promising avenue for early detection and prevention. In contrast to targeted approaches
[...] Read more.
Cancer continues to pose a considerable challenge to global health. In the search for innovative strategies to combat this complex enemy, the concept of universal cancer screening has emerged as a promising avenue for early detection and prevention. In contrast to targeted approaches that focus on specific populations or high-risk individuals, universal screening seeks to cast a wide net to detect incipient malignancies in different demographic groups. This paradigm shift in cancer care underscores the importance of comprehensive screening programs that go beyond conventional boundaries. As our understanding of the complex molecular and genetic basis of cancer deepens, the need to develop comprehensive screening methods becomes increasingly apparent. In this article, we look at the rationale and potential benefits of universal cancer screening.
Full article
(This article belongs to the Special Issue Biomarkers for the Early Detection and Treatment of Cancers)
►▼
Show Figures
Figure 1
Open AccessArticle
Responses to Medical Treatment in 192 Patients with Pancreatic Neuroendocrine Neoplasms Referred to the Copenhagen Neuroendocrine Tumour Centre in 2000–2020
by
Sofie Skovlund Petersen, Stine Møller, Cecilie Slott, Jesper Krogh, Carsten Palnæs Hansen, Andreas Kjaer, Pernille Holmager, Peter Oturai, Rajendra Singh Garbyal, Seppo W. Langer, Ulrich Knigge and Mikkel Andreassen
Cancers 2024, 16(6), 1190; https://doi.org/10.3390/cancers16061190 - 18 Mar 2024
Abstract
Background: Given the rarity and heterogeneity of pancreatic neuroendocrine neoplasms (pNEN), treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence. Aim: To investigate overall survival (OS), median progression-free survival (mPFS), and prognostic factors associated with the most common medical
[...] Read more.
Background: Given the rarity and heterogeneity of pancreatic neuroendocrine neoplasms (pNEN), treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence. Aim: To investigate overall survival (OS), median progression-free survival (mPFS), and prognostic factors associated with the most common medical treatments for pNEN. Methods: Retrospective single-center study encompassing patients diagnosed and monitored between 2000 and 2020 (n = 192). Results: Median OS was 36 (95% CI: 26–46) months (99 months for grade (G) 1, 62 for G2, 14 for G3, and 10 for neuroendocrine carcinomas). Patients treated with somatostatin analogues (SSA) (n = 59, median Ki-67 9%) had an mPFS of 28 months. Treatment line (HR (first line as reference) 4.1, 95% CI: 1.9–9.1, p ≤ 0.001) emerged as an independent risk factor for time to progression. Patients with a Ki-67 index ≥10% (n = 28) had an mPFS of 27 months. Patients treated with streptozocin/5-fluorouracil (STZ/5FU) (n = 70, first-line treatment n = 68, median Ki-67 10%) had an mPFS of 20 months, with WHO grade serving as an independent risk factor (HR (G1 (n = 8) vs. G2 (n = 57)) 2.8, 95% CI: 1.1–7.2, p-value = 0.031). Median PFS was 21 months for peptide receptor radionuclide therapy (PRRT) (n = 41, first line n = 2, second line n = 29, median Ki-67 8%), 5 months for carboplatin and etoposide (n = 66, first-line treatment n = 60, median Ki-67 80%), and 3 months for temozolomide-based therapy (n = 56, first-line treatment n = 17, median Ki-67 30%). Conclusion: (1) Overall survival was, as expected, highly dependent on grade; (2) median PFS for SSA was around 2.5 years without difference between tumors with Ki-67 above or below 10%; (3) STZ/5FU as first-line treatment exhibited a superior mPFS of 20 months compared to what has historically been reported for targeted treatments; (4) PRRT in G2 pNEN achieved an mPFS similar to first-line chemotherapy; and (5) limited treatment efficacy was observed in high-grade tumors when treated with carboplatin and etoposide or temozolomide.
Full article
(This article belongs to the Special Issue Neuroendocrine Tumors: From Diagnosis to Therapy)
►▼
Show Figures
Figure 1
Open AccessArticle
Early Onset of Lung Cancer in Small Areas as a Signature of Point Pollution Sources
by
Ettore Bidoli
Cancers 2024, 16(6), 1189; https://doi.org/10.3390/cancers16061189 - 18 Mar 2024
Abstract
The impact of air pollution on lung cancer (LC) is difficult to detect in low-populated areas due to the potentially unfocused detection of pollutants and/or limited statistical power. This study identified and measured the harmful effect of pollution in small areas by considering
[...] Read more.
The impact of air pollution on lung cancer (LC) is difficult to detect in low-populated areas due to the potentially unfocused detection of pollutants and/or limited statistical power. This study identified and measured the harmful effect of pollution in small areas by considering the early onset of LC as a signature of pollution. This novel method requires a Bayesian standard curve calculated from the median age at LC onset and the corresponding median age of reference populations. Similar medians gathered from the area/s under investigation permits a probabilistic comparison with the standard curve. Statistically significant divergences can be interpreted as early or late LC onset. The method is exemplified in the Trieste municipality (northeast Italy) using data from the Friuli Venezia Giulia Cancer Registry (study population) and from the International Agency for Research on Cancer (reference population). Early LC onset has been observed near the pollution sources. Within 600 m of the iron foundry, onset ranged between 3.2 and 7.7 years earlier in men and between 11.7 and 16.8 years earlier in women. Near the shipyard, early onset was around 4 years in men and 7 years in women, while in the industrial area, early onset was 5 years in women only. Examining early LC onset may speed up the investigation of potential environmental hazards.
Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
►▼
Show Figures
Figure 1
Open AccessSystematic Review
Investigating the Efficacy of EGFR-TKIs and Anti-VEGFR Combination in Advanced Non-Small Cell Lung Cancer: A Meta-Analysis
by
Prashant Sakharkar, Sonali Kurup, Subrata Deb, Kaitlin Assaad, Dayna Gesinski and Erysa J. Gayle
Cancers 2024, 16(6), 1188; https://doi.org/10.3390/cancers16061188 - 18 Mar 2024
Abstract
Introduction: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with anti-vascular endothelial growth factor receptor (VEGFR) agents have shown improved survival outcomes in recent studies. However, its efficacy related to survival outcomes as a first- or second-line agent and based
[...] Read more.
Introduction: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with anti-vascular endothelial growth factor receptor (VEGFR) agents have shown improved survival outcomes in recent studies. However, its efficacy related to survival outcomes as a first- or second-line agent and based on generations remains to be explored. This study estimated the survival outcomes of EGFR-TKIs plus anti-VEGFR in combination in defined populations of advanced non-small cell lung cancer (NSCLC) patients overall, as a first- or second line of treatment, with different generations of EGFR-TKIs and EGFR-TKIs plus bevacizumab combination as a subgroup. Methods: A literature search was conducted using PubMed, SCOPUS, Cochrane Library, and ClinicalTrials.gov databases through June 2023 to identify primary research reporting the survival outcomes of EGFR-TKIs in combination with anti-VEGFR agents in patients with advanced NSCLC. Studies that were single-arm, published in non-English languages, and had missing data on survival outcomes were excluded. A meta-analysis was conducted to generate pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS). Methodological quality and risk of bias in studies were assessed using the Cochrane Handbook for Systematic Reviews of Interventions risk of bias tool. Results: A total of 20 randomized controlled trials were included in the qualitative synthesis, and 11 (2182 participants) were included in the meta-analysis. Patients’ median age ranged from 58 to 68 years; 36% to 70% of patients were female; most of them had IIIa/b to IV stage cancer. In meta-analyses, the EGFR-TKIs plus anti-VEGFR combination resulted in improved PFS (HR, 0.73; 95% CI: 0.61, 0.86; p < 0.00001) in patients with advanced NSCLC but had no impact on OS (HR, 0.93; 95% CI: 0.79, 1.10; p = 0.41). The first line of treatment and first-generation EGFR-TKIs with the combination also improved the PFS (HR, 0.64; 95% CI: 0.57, 0.71; p < 0.00001; HR, 0.63; 95% CI: 0.56, 0.71; p < 0.00001) respectively, however, had no impact on OS. Conclusions: Our meta-analysis indicated EGFR-TKIs with anti-VEGFR in combination not only improved overall PFS but also showed similar results to a first line and first-generation agent compared to EGFR-TKI alone.
Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
►▼
Show Figures
Figure 1
Open AccessArticle
Exercise Suppresses Head and Neck Squamous Cell Carcinoma Growth via Oncostatin M
by
Takuya Yoshimura, Yuka Hirano, Taiji Hamada, Seiya Yokoyama, Hajime Suzuki, Hirotaka Takayama, Hirono Migita, Takayuki Ishida, Yasunori Nakamura, Masahiro Ohsawa, Akihiro Asakawa, Kiyohide Ishihata and Akihide Tanimoto
Cancers 2024, 16(6), 1187; https://doi.org/10.3390/cancers16061187 - 18 Mar 2024
Abstract
Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers,
[...] Read more.
Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study. Just prior to transplantation, blood was collected from the mice, and the levels of myokines were measured by ELISA. Oncostatin M (OSM), a selected myokine, was added to HSC-3-M3 cells, after which the cell proliferation ability, cell cycle, and protein expression were analyzed in vitro. Tumor cell viability was lower (control: 100%, exercise: 75%), tumors were smaller (control: 26.2 mm3, exercise: 6.4 mm3), and survival was longer in the exercise group than in the control group in vivo. OSM inhibited HSC-3-M3 cell proliferation in a concentration-dependent manner in vitro. The addition of OSM increased the proportion of cells in the G0/G1 phase, decreased the proportion of cells in the G2/M phase, and increased the expression of the CDK inhibitors p21 and p27. These results indicate that exercise may directly inhibit the proliferation of HNSCC cell lines via OSM.
Full article
(This article belongs to the Section Cancer Pathophysiology)
►▼
Show Figures
Figure 1
Open AccessArticle
Natural Killer Cell Dysfunction in Premenopausal BRCA1 Mutation Carriers: A Potential Mechanism for Ovarian Carcinogenesis
by
Shaun Haran, Kantaraja Chindera, May Sabry, Nafisa Wilkinson, Rupali Arora, Agnieszka Zubiak, Thomas E. Bartlett, Iona Evans, Allison Jones, Daniel Reisel, Chiara Herzog, Twana Alkasalias, Mark Newman, Jaeyeon Kim, Angelique Flöter Rådestad, Kristina Gemzell-Danielsson, Adam N. Rosenthal, Louis Dubeau, Mark W. Lowdell and Martin Widschwendter
Cancers 2024, 16(6), 1186; https://doi.org/10.3390/cancers16061186 - 18 Mar 2024
Abstract
Background: Tissue-specificity for fimbrial fallopian tube ovarian carcinogenesis remains largely unknown in BRCA1 mutation carriers. We aimed to assess the cell autonomous and cell-nonautonomous implications of a germline BRCA1 mutation in the context of cancer immunosurveillance of CD3− CD56+ natural killer
[...] Read more.
Background: Tissue-specificity for fimbrial fallopian tube ovarian carcinogenesis remains largely unknown in BRCA1 mutation carriers. We aimed to assess the cell autonomous and cell-nonautonomous implications of a germline BRCA1 mutation in the context of cancer immunosurveillance of CD3− CD56+ natural killer (NK) cells. Methods: Premenopausal BRCA1 mutation carriers versus age-matched non-carriers were compared. Daily urinary 5β-pregnanediol levels were used to determine progesterone metabolomics across an ovarian cycle. Using peripherally acquired NK cells the cell-mediated cytotoxicity of tumor targets (OVCAR-3, K-562) was determined using live cellular impedance (xCELLigence®) and multicolor flow cytometry. Hypoxia-inducible factor 1-alpha (HIF-1α) immunohistochemistry of cancer-free fallopian tube specimens allowed a comparison of proximal versus distal portions. Utilizing these findings the role of environmental factors relevant to the fimbrial fallopian tube (progesterone, hypoxia) on NK cell functional activity were studied in an ovarian phase-specific manner. Results: BRCA1 mutation carriers demonstrate a differential progesterone metabolome with a phase-specific reduction of peripheral NK cell functional activity. Progesterone exposure further impairs NK cell-mediated cytotoxicity in a dose-dependent manner, which is reversed with the addition of mifepristone (1.25 µM). The fimbrial fallopian tube demonstrated significantly higher HIF-1α staining, particularly in BRCA1 mutation carriers, reflecting a site-specific ‘hypoxic niche’. Exposure to hypoxic conditions (1% O2) can further impair tumor cytotoxicity in high-risk carriers. Conclusions: Phase-specific differential NK cell activity in BRCA1 mutation carriers, either systemically or locally, may favor site-specific pre-invasive carcinogenesis. These cumulative effects across a reproductive lifecycle in high-risk carriers can have a detrimental effect further supporting epidemiological evidence for ovulation inhibition.
Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
►▼
Show Figures
Figure 1
Open AccessArticle
EMT Dynamics in Lymph Node Metastasis of Oral Squamous Cell Carcinoma
by
Yasmine Ghantous, Shiraz Mozalbat, Aysar Nashef, Murad Abdol-Elraziq, Shiran Sudri, Shareef Araidy, Hagar Tadmor and Imad Abu El-naaj
Cancers 2024, 16(6), 1185; https://doi.org/10.3390/cancers16061185 - 18 Mar 2024
Abstract
Background: Epithelial–mesenchymal transition (EMT) enables tumor cell invasion and metastasis. Many studies have demonstrated the critical role of EMT in lymph node metastasis in oral squamous cell carcinoma (OSCC). During EMT, epithelial cancer cells lose intercellular adhesion and apical–basal polarity and acquire mesenchymal
[...] Read more.
Background: Epithelial–mesenchymal transition (EMT) enables tumor cell invasion and metastasis. Many studies have demonstrated the critical role of EMT in lymph node metastasis in oral squamous cell carcinoma (OSCC). During EMT, epithelial cancer cells lose intercellular adhesion and apical–basal polarity and acquire mesenchymal properties such as motility and invasiveness. A significant feature of EMT is cadherin switching, involving the downregulation of E-cadherin and upregulation of N-cadherin. The TGF-β/SMAD pathway can also induce EMT. We aimed to evaluate EMT markers as predictors of lymph node metastasis in OSCC. Methods: We performed genetic profiling of 159 primary OSCCs from TCGA and analyzed the expression of EMT markers, including cadherin switch genes (CDH1, CDH2), and TGF-β/SMAD pathway genes. Samples were divided into advanced (stage III–IV) and early (stage I–II) stage groups. Differential expression analysis was performed, as well as an independent validation study containing fresh OSCC samples. Results: TGF-β/SMAD pathway genes such as SMAD6 were upregulated in advanced stage tumors. N-cadherin and SNAIL2 were overexpressed in node-positive tumors. Keratins were downregulated in these groups. Conclusion: Our findings demonstrate that EMT marker expression correlates with lymph node metastasis in OSCC. Developing therapies targeting regulators such as N-cadherin may prevent metastasis and improve outcomes.
Full article
(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection)
►▼
Show Figures
Figure 1
Open AccessArticle
TP53 and/or BRCA1 Mutations Based on CtDNA Analysis as Prognostic Biomarkers for Primary Triple-Negative Breast Cancer
by
Akiko Arimura, Kazuko Sakai, Kazuhisa Kaneshiro, Takafumi Morisaki, Saori Hayashi, Kimihisa Mizoguchi, Mai Yamada, Masaya Kai, Mayumi Ono, Kazuto Nishio, Masafumi Nakamura and Makoto Kubo
Cancers 2024, 16(6), 1184; https://doi.org/10.3390/cancers16061184 - 18 Mar 2024
Abstract
Precise biomarkers for predicting the therapeutic efficacy of molecularly targeted drugs are limited at the protein level; thus, it has been important to broadly scrutinize individual cancer driver gene mutations for effective cancer treatments. Multiplex cancer genome profiling can comprehensively identify gene mutations
[...] Read more.
Precise biomarkers for predicting the therapeutic efficacy of molecularly targeted drugs are limited at the protein level; thus, it has been important to broadly scrutinize individual cancer driver gene mutations for effective cancer treatments. Multiplex cancer genome profiling can comprehensively identify gene mutations that are therapeutic targets using next-generation sequencing (NGS). In addition, circulating tumor DNA (ctDNA) is a DNA fragment released into the blood by tumor cell-derived cell death or apoptosis. Liquid biopsy with ctDNA is a novel clinical test for identifying genetic mutations in an entire population noninvasively, in real-time, and heterogeneously. Although there are several reports on ctDNA, fewer have evaluated ctDNA with NGS before an initial treatment for breast cancer patients. Therefore, we examined whether analyzing tumor-associated gene mutations in primary breast cancer based on ctDNA could serve as a biomarker for prognosis and optimal treatment selection. Ninety-five primary breast cancer patients treated at our department from January 2017 to October 2020 were included. Pretreatment plasma samples were subjected to NGS analysis of ctDNA, and correlations with patients’ clinicopathological characteristics were evaluated. Fifty-nine (62.1%) patients were positive for ctDNA. ctDNA tended to be positive in hormone receptor-negative, and TP53 (34%), BRCA1 (20%), and BRCA2 (17%) gene mutations were more frequent. Regarding recurrence-free survival, the prognosis was poor in the TP53 and/or BRCA1 mutation-positive groups, especially in triple-negative breast cancer (TNBC) patients. In conclusion, the results of this study indicate that ctDNA with liquid biopsy could identify the poor prognosis group before treatment among TNBC patients and for those for whom optimal treatment selection is desirable; additionally, optimal treatment could be selected according to the ctDNA analysis results.
Full article
(This article belongs to the Special Issue Liquid Biopsy in Cancer 2.0)
►▼
Show Figures
Figure 1
Open AccessReview
Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression
by
Yan Hu, Dan Jones, Ashwini K. Esnakula, Somashekar G. Krishna and Wei Chen
Cancers 2024, 16(6), 1183; https://doi.org/10.3390/cancers16061183 - 18 Mar 2024
Abstract
The malignant progression of pancreatic cystic lesions (PCLs) remains understudied with a knowledge gap, yet its exploration is pivotal for effectively stratifying patient risk and detecting cancer at its earliest stages. Within this review, we delve into the latest discoveries on the molecular
[...] Read more.
The malignant progression of pancreatic cystic lesions (PCLs) remains understudied with a knowledge gap, yet its exploration is pivotal for effectively stratifying patient risk and detecting cancer at its earliest stages. Within this review, we delve into the latest discoveries on the molecular level, revealing insights into the IPMN molecular landscape and revised progression model, associated histologic subtypes, and the role of inflammation in the pathogenesis and malignant progression of IPMN. Low-grade PCLs, particularly IPMNs, can develop into high-grade lesions or invasive carcinoma, underscoring the need for long-term surveillance of these lesions if they are not resected. Although KRAS and GNAS remain the primary oncogenic drivers of neoplastic development in IPMNs, additional genes that are important in tumorigenesis have been recently identified by whole exome sequencing. A more complete understanding of the genes involved in the molecular progression of IPMN is critical for effective monitoring to minimize the risk of malignant progression. Complicating these strategies, IPMNs are also frequently multifocal and multiclonal, as demonstrated by comparative molecular analysis. Algorithms for preoperative cyst sampling and improved radiomic techniques are emerging to model this spatial and temporal genetic heterogeneity better. Here, we review the molecular pathology of PCLs, focusing on changes associated with malignant progression. Developing models of molecular risk stratification in PCLs which can complement radiologic and clinical features, facilitate the early detection of pancreatic cancer, and enable the development of more personalized surveillance and management strategies are summarized.
Full article
(This article belongs to the Special Issue Histology and Pathology of Pancreatic Cancer)
►▼
Show Figures
Figure 1
Open AccessSystematic Review
Systemic Chemotherapy in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery: Systematic Review and Meta-Analysis
by
Marco Tonello, Carola Cenzi, Elisa Pizzolato, Riccardo Fiscon, Paola Del Bianco, Pierluigi Pilati and Antonio Sommariva
Cancers 2024, 16(6), 1182; https://doi.org/10.3390/cancers16061182 - 18 Mar 2024
Abstract
Background. For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on
[...] Read more.
Background. For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on the survival and surgical complications of patients treated with CRS-HIPEC. Methods. After a systematic search in MEDLINE, Cochrane Database of Systematic Reviews, Scopus, Web of Science and Embase, a meta-analysis was performed to compare postoperative complications, disease-free survival (DFS) and overall survival (OS) according to SC administration and timing. PROSPERO: CRD42023478977. Results. Of 1203 studies screened, 15 were included in the meta-analysis (4523 patients). Post-operative SC was associated with increased overall survival (post-SC vs. no post-SC: HR 0.81, p = 0.00001, I2 = 0%; pre-SC vs. post-SC: HR 0.65, p = 0.01, I2 = 28%), whereas SC (pre or post) or pre-SC compared to surgery alone was not (SC vs. no SC: p = 0.29, I2 = 80%; pre-SC vs. no pre-SC: p = 0.59, I2 = 58%). Similar results were seen for DFS. SC was not associated with an increased complication rate (p = 0.47, I2 = 64%). Conclusions. Systemic chemotherapy administration in patients undergoing radical surgery for colorectal peritoneal metastases is associated with increased survival only in the adjuvant/post-operative setting. Considering the limitations of the included studies, further trials are needed to answer this unresolved question.
Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
►▼
Show Figures
Figure 1
Open AccessCorrection
Correction: Huang et al. Systemic Anticoagulation and Inpatient Outcomes of Pancreatic Cancer: Real-World Evidence from U.S. Nationwide Inpatient Sample. Cancers 2023, 15, 1985
by
Yen-Min Huang, Hsuan-Jen Shih, Yi-Chan Chen, Tsan-Yu Hsieh, Che-Wei Ou, Po-Hsu Su, Shih-Ming Chen, Yun-Cong Zheng and Li-Sung Hsu
Cancers 2024, 16(6), 1181; https://doi.org/10.3390/cancers16061181 - 18 Mar 2024
Abstract
In the original publication [...]
Full article
Open AccessArticle
PIP4K2B Protein Regulation by NSD1 in HPV-Negative Head and Neck Squamous Cell Carcinoma
by
Iuliia Topchu, Igor Bychkov, Ekaterina Roshchina, Petr Makhov and Yanis Boumber
Cancers 2024, 16(6), 1180; https://doi.org/10.3390/cancers16061180 - 17 Mar 2024
Abstract
Head and neck squamous cell carcinoma (HNSCC) ranks among the most prevalent global cancers. Despite advancements in treatments, the five-year survival rate remains at approximately 66%. The histone methyltransferase NSD1, known for its role in catalyzing histone H3 lysine 36 di-methylation (H3K36me2
[...] Read more.
Head and neck squamous cell carcinoma (HNSCC) ranks among the most prevalent global cancers. Despite advancements in treatments, the five-year survival rate remains at approximately 66%. The histone methyltransferase NSD1, known for its role in catalyzing histone H3 lysine 36 di-methylation (H3K36me2), emerges as a potential oncogenic factor in HNSCC. Our study, employing Reverse Phase Protein Array (RPPA) analysis and subsequent validation, reveals that PIP4K2B is a key downstream target of NSD1. Notably, PIP4K2B depletion in HNSCC induces downregulation of the mTOR pathway, resulting in diminished cell growth in vitro. Our investigation highlights a direct, positive regulatory role of NSD1 on PIP4K2B gene transcription through an H3K36me2-dependent mechanism. Importantly, the impact of PIP4K2B appears to be context-dependent, with overexpression rescuing cell growth in laryngeal HNSCC cells but not in tongue/hypopharynx cells. In conclusion, our findings implicate PIP4K2B as a novel NSD1-dependent protein in HNSCC, suggesting its potential significance for laryngeal cancer cell survival. This insight contributes to our understanding of the molecular landscape in HNSCC and establishes PIP4KB as a promising target for drug development.
Full article
(This article belongs to the Special Issue Molecular Mechanisms in Head and Neck Cancer)
►▼
Show Figures
Figure 1
Open AccessReview
Robotic Bronchoscopy in Lung Cancer Diagnosis
by
Vasileios S. Skouras, Ioannis Gkiozos, Andriani G. Charpidou and Konstantinos N. Syrigos
Cancers 2024, 16(6), 1179; https://doi.org/10.3390/cancers16061179 - 17 Mar 2024
Abstract
Background: The widespread use of chest CT has increased the number of detected pulmonary nodules. Nodules with intermediate risk of malignancy warrant further evaluation with PET-CT or sampling. Although sampling with conventional bronchoscopy presents lower complication rates compared to transthoracic needle biopsy (TTNB),
[...] Read more.
Background: The widespread use of chest CT has increased the number of detected pulmonary nodules. Nodules with intermediate risk of malignancy warrant further evaluation with PET-CT or sampling. Although sampling with conventional bronchoscopy presents lower complication rates compared to transthoracic needle biopsy (TTNB), it is limited by the inability to reach distal airways. To overcome this shortcoming, a new bronchoscopic technique named robotic bronchoscopy (RB) has emerged. Methods: A literature review was used to clarify the rationale behind RB emergence, describe RB procedure, and summarize data regarding its efficacy and safety. Results: The FDA has approved three RB platforms for clinical use. RB is safe, presenting a mortality and complication rate of 0% and 0–8.1%, respectively. Common complications include pneumothorax (0–5.7%) and minor bleeding (0–3.2%). However, its diagnostic yield remains lower than that of TTNB. Conclusions: RB is a promising bronchoscopic technique that aims to overcome the limitations of conventional bronchoscopy and improve upon the current techniques of guided bronchoscopy for the investigation of pulmonary nodules. Despite the lower complication rate, current evidence suggests a lower diagnostic yield compared to TTNB. Additional studies are required to adequately evaluate the role of RB in the diagnosis of pulmonary nodules.
Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
►▼
Show Figures
Figure 1
Open AccessArticle
The Effect of Retinoic Acid on Arsenite-Transformed Malignant UROtsa Bladder Cancer Cells: In Vitro Model of Basal Muscle-Invasive Bladder Cancer
by
Sarmad Al-Marsoummi, Aaron A. Mehus, Scott H. Garrett, Donald A. Sens and Seema Somji
Cancers 2024, 16(6), 1178; https://doi.org/10.3390/cancers16061178 - 17 Mar 2024
Abstract
Bladder cancer (BC) is the eighth most common cause of cancer death in the United States of America. BC is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Genetically, MIBCs are categorized into the more aggressive basal subtype or less
[...] Read more.
Bladder cancer (BC) is the eighth most common cause of cancer death in the United States of America. BC is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Genetically, MIBCs are categorized into the more aggressive basal subtype or less aggressive luminal subtype. All-trans retinoic acid (tretinoin), the ligand for the RAR-RXR retinoic acid receptor, is clinically used as a differentiation therapy in hematological malignancies. This study aims to determine the effects of retinoic acid on arsenite-transformed malignant urothelial cells (UROtsa As), serving as a model for basal muscle-invasive bladder cancer. We treated three independent isolates of arsenite-transformed malignant human urothelial UROtsa cells (UROtsa As) with tretinoin for 48 h. Cell viability, proliferation, and apoptosis were analyzed using crystal violet staining and flow cytometry. mRNA and protein level analyses were performed using RT-qPCR and the Simple Western™ platform, respectively. Tretinoin was found to reduce cell proliferation and urosphere formation, as well as decrease the expression of basal markers (KRT1, KRT5, KRT6, EGFR) and increase the expression of luminal differentiation markers (GATA3, FOXA1). Mechanistically, the antiproliferative effect of tretinoin was attributed to the downregulation of c-myc. Our results suggest that targeting the retinoic acid pathway can diminish the aggressive behavior of basal muscle-invasive urothelial cancer and may enhance patient survival.
Full article
(This article belongs to the Section Molecular Cancer Biology)
►▼
Show Figures
Figure 1
Journal Menu
► ▼ Journal Menu-
- Cancers Home
- Aims & Scope
- Editorial Board
- Reviewer Board
- Topical Advisory Panel
- Instructions for Authors
- Special Issues
- Topics
- Sections & Collections
- Article Processing Charge
- Indexing & Archiving
- Editor’s Choice Articles
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Society Collaborations
- Conferences
- Editorial Office
Journal Browser
► ▼ Journal BrowserHighly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Brain Sciences, Cancers, JCM, JVD, Neurology International
Inflammation in Neuro-Oncological Diseases and in Neuro-Vascular Diseases
Topic Editors: Erdem Güresir, Johannes Wach, Martin VychopenDeadline: 31 March 2024
Topic in
Biomedicines, BioMedInformatics, Cancers, JCM, Cells, Current Oncology
Cancer Immunity and Immunotherapy: Early Detection, Diagnosis, Systemic Treatments, Novel Biomarkers, and Resistance Mechanisms
Topic Editors: Tao Jiang, Yongchang ZhangDeadline: 20 April 2024
Topic in
Bioengineering, Biomolecules, Cancers, Diseases, Nanomaterials, Pharmaceutics
Dynamic Nano-Biomaterials in Tissue Regeneration and Cancer Therapies
Topic Editors: Ramar Thangam, Heemin Kang, Bibin G. Anand, Ramachandran Vijayan, Venugopal KrishnanDeadline: 15 May 2024
Topic in
Biomedicines, Cancers, JFB, Nanomaterials, Polymers
Advanced Functional Materials for Regenerative Medicine
Topic Editors: Antonino Morabito, Luca ValentiniDeadline: 6 June 2024
Conferences
Special Issues
Special Issue in
Cancers
Pediatric and AYA Sarcoma and Intermediate Tumors
Guest Editor: Yoshihiro NishidaDeadline: 25 March 2024
Special Issue in
Cancers
Targeting Signal Transduction Pathways in Cancer
Guest Editors: Mohd W. Nasser, Shahab Uddin, Klaus Podar, Martin SattlerDeadline: 31 March 2024
Special Issue in
Cancers
The Role of Tunneling Nanotubes in Intercellular Communication and Pathophysiology of Cancer
Guest Editor: Emil LouDeadline: 25 April 2024
Special Issue in
Cancers
Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement
Guest Editor: Gianluca PellinoDeadline: 30 April 2024
Topical Collections
Topical Collection in
Cancers
Drug Resistance and Novel Therapies in Cancers
Collection Editor: Zhixiang Wang