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Cancer Therapy: Where We Are and Where We Need to Go

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 15437

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Special Issue Editors

Dr. Hao Zhang

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Guest Editor

Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
Interests: bioinformatics; tumor microenvironment; biomarker; tumorigenic mechanism
Special Issues, Collections and Topics in MDPI journals

Dr. Nan Zhang

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Guest Editor

Hubei Bioinformatics and Molecular Imaging Key Laboratory, Center for Artificial Intelligence Biology, Department of Bioinformatics and Systems Biology, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
Interests: bioinformatics; tumor microenvironment; biomarker; tumorigenic mechanism
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Youwen Zhou

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Guest Editor

Department of Dermatology & Skin Science, Faculty of Medicine, University of British Columbia, Vancouver, BC V5Z 4E8, Canada
Interests: vitiligo and skin pigmentation; melanoma and skin lymphoma; preclinical and clinical therapeutic research

Special Issue Information

Dear Colleagues,

In this era of precision medicine and exciting advances, drug resistance remains an important obstacle to cancer treatment. The development of targeted therapy based on increasingly revealed pathogenic mechanisms of cancer has made contributions to overcoming drug resistance. The use of model organisms in target discovery and validation of small molecule drugs is becoming commonplace. A critical objective of this topic is the target discovery and validation of small-molecule drugs. Another important aspect of this topic is the description and elucidation of novel molecular targets and pathways and insights into precision medicine.

Besides, immunotherapy, represented by immune checkpoint inhibitors (ICIs) and CAR-T therapy, has led to better therapeutic outcomes. However, there are still quite a lot of patients suffering from severe side effects and ineffective treatment outcomes. Although some candidate biomarkers, including PD-L1, tumor mutation burden (TMB), interferon-gamma (IFN-g), and microsatellite instability (MSI), could facilitate the clinical selection of patients for ICI treatment, these approaches are hampered by moderate accuracy and limited scope of application. To this end, identifying new immunotherapy biomarkers, mining resistance mechanisms, and exploring potential targets for enhancing immunotherapy efficacy are urgent, as this could facilitate the selection of potential immunotherapy beneficiaries.

Potential topics include but are not limited to the following:

New technologies or methods employed to discover biomarkers for cancer immunotherapy.
Integrated genomic analysis identifies clinically relevant subtypes of patients sensitive to cancer immunotherapy.
Novel molecular mechanisms involved in the response or sensibility of cancer immunotherapy.
Immune neoantigen of tumor involved in the immune response during cancer immunotherapy.
Bioinformatics research with validation to identify novel biomarkers and models based on cancer immunotherapy patients.
Pathogenic mechanisms of cancer in drug resistance.
Novel targeted therapy of cancer based on newly defined molecular mechanisms.
Biomarkers for cancer development.
The target discovery and validation of small-molecule drugs.
Machine learning-based predictive and prognostic model.

Dr. Hao Zhang
Dr. Nan Zhang
Prof. Dr. Youwen Zhou
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (9 papers)

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Research

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11 pages, 238 KiB

Open AccessArticle

Comparing Molnupiravir to Nirmatrelvir/Ritonavir (Paxlovid) in the Treatment of Mild-to-Moderate COVID-19 in Immunocompromised Cancer Patients

by Andrea J. Haddad, Ray Y. Hachem, Mohamed Moussa, Ying Jiang, Hiba R. Dagher, Patrick Chaftari, Anne-Marie Chaftari and Issam I. Raad

Cancers 2024, 16(5), 1055; https://doi.org/10.3390/cancers16051055 - 5 Mar 2024

Viewed by 1136

Abstract

Background: Nirmatrelvir/Ritonavir has been shown to reduce the risk of COVID-19 progression by 88% compared to placebo, while Molnupiravir reduced it by 31%. However, these two agents have not been compared head-to-head. We therefore compared the safety and efficacy of both agents for the treatment of mild-to-moderate COVID-19 in immunocompromised cancer patients. Methods: We identified 240 cancer patients diagnosed with COVID-19 and treated with Molnupiravir or Nirmatrelvir/Ritonavir. Patients were matched using a 1:2 ratio based on age group (18–64 years vs. ≥65) and type of cancer. The collected data included demographics, comorbidities, and treatment outcome. Results: Both groups had comparable characteristics and presenting symptoms. However, dyspnea was more prevalent in the Molnupiravir group, while sore throat was more prevalent in the Nirmatrelvir/Ritonavir group. The rate of disease progression was comparable in both groups by univariate and multivariable analysis. Treatment with Molnupiravir versus Nirmatrelvir/Ritonavir revealed no significant difference in disease progression by multivariable analysis (adjusted OR = 1.31, 95% CI: 0.56–3.14, p = 0.70). Patients who received Nirmatrelvir/Ritonavir, however, were significantly more prone to having drug–drug interactions/adverse events (30% vs. 0%, p < 0.0001). Conclusions: In the treatment of mild-to-moderate COVID-19 in cancer patients, Molnupiravir was comparable to Nirmatrelvir/Ritonavir in preventing progression to severe disease/death and rebound events, and it had a superior safety profile. Full article

(This article belongs to the Special Issue Cancer Therapy: Where We Are and Where We Need to Go)

19 pages, 4288 KiB

Open AccessArticle

The Mechanism of Oxymatrine Targeting miR-27a-3p/PPAR-γ Signaling Pathway through m6A Modification to Regulate the Influence on Hemangioma Stem Cells on Propranolol Resistance

by Yuxin Dai, Mingke Qiu, Shenglai Zhang, Jingyu Peng, Xin Hou, Jie Liu, Feifei Li and Jingmin Ou

Cancers 2023, 15(21), 5213; https://doi.org/10.3390/cancers15215213 - 30 Oct 2023

Viewed by 1070

Abstract

Objective: The proliferation and migration of hemangioma stem cells (HemSCs) induced apoptosis and adipose differentiation as well as increased the sensitivity of HemSCs to propranolol (PPNL). MiR-27a-3p negatively controlled the peroxisome-proliferator-activated receptor γ (PPAR-γ) level, counteracting the effect of PPAR-γ on HemSC progression and PPNL resistance. OMT accelerated HemSC progression and adipocyte differentiation via modulating the miR-27a-3p/PPAR-γ axis, inhibiting HemSC resistance to PPNL. In tumor-forming experiments, OMT exhibited a dose-dependent inhibitory effect on the volume of IH PPNL-resistant tumors, which was partially dependent on the regulation of m6A methylation transfer enzyme METTL3 and the miR-27a-3p/PPAR-γ axis, thereby inducing apoptosis. Conclusions: We conclude that OMT regulates IH and influences PPNL resistance via targeting the miR-27a-3p/PPAR-γ signaling pathway through m6A modification. Full article

(This article belongs to the Special Issue Cancer Therapy: Where We Are and Where We Need to Go)

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10 pages, 923 KiB

Open AccessArticle

Access to Care and Healthcare Quality Metrics for Patients with Advanced Genitourinary Cancers in Urban versus Rural Areas

by Haoran Li, Kamal Kant Sahu, Shruti Adidam Kumar, Nishita Tripathi, Nicolas Sayegh, Blake Nordblad, Beverly Chigarira, Sumati Gupta, Benjamin L. Maughan, Neeraj Agarwal and Umang Swami

Cancers 2023, 15(21), 5171; https://doi.org/10.3390/cancers15215171 - 27 Oct 2023

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Abstract

Compared to the urban population, patients in rural areas face healthcare disparities and experience inferior healthcare-related outcomes. To compare the healthcare quality metrics and outcomes between patients with advanced genitourinary cancers from rural versus urban areas treated at a tertiary cancer hospital, in this retrospective study, eligible patients with advanced genitourinary cancers were treated at Huntsman Cancer Institute, an NCI-Designated Comprehensive Cancer Center in Utah. Rural–urban commuting area codes were used to classify the patients’ residences as being in urban (1–3) or rural (4–10) areas. The straight line distances of the patients’ residences from the cancer center were also calculated and included in the analysis. The median household income data were obtained and calculated from “The Michigan Population Studies Center”, based on individual zip codes. In this study, 2312 patients were screened, and 1025 eligible patients were included for further analysis (metastatic prostate cancer (n = 679), metastatic bladder cancer (n = 184), and metastatic renal cell carcinoma (n = 162). Most patients (83.9%) came from urban areas, while the remainder were from rural areas. Both groups had comparable demographic profiles and tumor characteristics at baseline. The annual median household income of urban patients was $8604 higher than that of rural patients (p < 0.001). There were fewer urban patients with Medicare (44.9% vs. 50.9%) and more urban patients with private insurance (40.4% vs. 35.1%). There was no difference between the urban and rural patients regarding receiving systemic therapies, enrollment in clinical trials, or tumor genomic profiling. The overall survival rate was not significantly different between the two populations in metastatic prostate, bladder, and kidney cancer, respectively. As available in a tertiary cancer hospital, access to care can mitigate the difference in the quality of healthcare and clinical outcomes in urban versus rural patients. Full article

(This article belongs to the Special Issue Cancer Therapy: Where We Are and Where We Need to Go)

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16 pages, 6168 KiB

Open AccessArticle

CircRNA RNA hsa_circ_0008234 Promotes Colon Cancer Progression by Regulating the miR-338-3p/ETS1 Axis and PI3K/AKT/mTOR Signaling

by Dejun Wu, Yuqin Li, Anjun Xu, Wenqing Tang and Bo Yu

Cancers 2023, 15(7), 2068; https://doi.org/10.3390/cancers15072068 - 30 Mar 2023

Cited by 7 | Viewed by 1431

Abstract

Circular RNAs (circRNAs) have been shown to play a crucial role in cancer occurrence and progression. This present work investigated the link between hsa_circ_0008234 and colon cancer. Data retrieved from GSE172229 was used to compare the circRNA profiles of colon cancer and surrounding non-tumorous tissues. The amount of RNA and protein in the molecules was determined using quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. The cell proliferation ability was assessed using CCK8, EdU, colon formation, and nude mice tumorigenesis tests. Cell invasion and migration abilities were evaluated using transwell wound healing and mice lung metastasis model. Hsa_circ_0008234 piqued our interest because bioinformatics and qRT-PCR analyses revealed that it is upregulated in colon cancer tissue. Cell phenotypic studies suggest that hsa_circ_0008234 may significantly increase colon cancer cell aggressiveness. Mice experiments revealed that inhibiting hsa_circ_0008234 significantly reduced tumor growth and metastasis. Moreover, the fluorescence in situ hybridization experiment demonstrated that hsa_circ_0008234 is primarily found in the cytoplasm, implying that it potentially functions via a competitive endogenous RNA pathway. These findings indicated that hsa_circ_0008234 may act as a “molecular sponge” for miR-338-3p, increasing the expression of miR-338-target 3p’s ETS1. In addition, the traditional oncogenic pathway PI3K/AKT/mTOR signaling was found to be the potential downstream pathway of the hsa_circ_0008234/miR-338-3p/ETS1 axis. In conclusion, hsa_circ_0008234 increases colon cancer proliferation, infiltration, and migration via the miR-338-3p/ETS1/PI3K/AKT axis; therefore, it could serve as a target and a focus for colon cancer therapy. Full article

(This article belongs to the Special Issue Cancer Therapy: Where We Are and Where We Need to Go)

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Review

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27 pages, 2087 KiB

Open AccessReview

The Future of Targeted Therapy for Leiomyosarcoma

by Ryan A. Denu, Amanda M. Dann, Emily Z. Keung, Michael S. Nakazawa and Elise F. Nassif Haddad

Cancers 2024, 16(5), 938; https://doi.org/10.3390/cancers16050938 - 26 Feb 2024

Viewed by 2877

Abstract

Leiomyosarcoma (LMS) is an aggressive subtype of soft tissue sarcoma that arises from smooth muscle cells, most commonly in the uterus and retroperitoneum. LMS is a heterogeneous disease with diverse clinical and molecular characteristics that have yet to be fully understood. Molecular profiling has uncovered possible targets amenable to treatment, though this has yet to translate into approved targeted therapies in LMS. This review will explore historic and recent findings from molecular profiling, highlight promising avenues of current investigation, and suggest possible future strategies to move toward the goal of molecularly matched treatment of LMS. We focus on targeting the DNA damage response, the macrophage-rich micro-environment, the PI3K/mTOR pathway, epigenetic regulators, and telomere biology. Full article

(This article belongs to the Special Issue Cancer Therapy: Where We Are and Where We Need to Go)

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24 pages, 1608 KiB

Open AccessReview

Exosomes—Promising Carriers for Regulatory Therapy in Oncology

by Teresa Maria Jóźwicka, Patrycja Maria Erdmańska, Agnieszka Stachowicz-Karpińska, Magdalena Olkiewicz and Wojciech Jóźwicki

Cancers 2024, 16(5), 923; https://doi.org/10.3390/cancers16050923 - 25 Feb 2024

Viewed by 1268

Abstract

Extracellular vesicles (EVs), including exosomes and microvesicles, together with apoptotic bodies form a diverse group of nanoparticles that play a crucial role in intercellular communication, participate in numerous physiological and pathological processes. In the context of cancer, they can allow the transfer of bioactive molecules and genetic material between cancer cells and the surrounding stromal cells, thus promoting such processes as angiogenesis, metastasis, and immune evasion. In this article, we review recent advances in understanding how EVs, especially exosomes, influence tumor progression and modulation of the microenvironment. The key mechanisms include exosomes inducing the epithelial–mesenchymal transition, polarizing macrophages toward protumoral phenotypes, and suppressing antitumor immunity. The therapeutic potential of engineered exosomes is highlighted, including their loading with drugs, RNA therapeutics, or tumor antigens to alter the tumor microenvironment. Current techniques for their isolation, characterization, and engineering are discussed. Ongoing challenges include improving exosome loading efficiency, optimizing biodistribution, and enhancing selective cell targeting. Overall, exosomes present promising opportunities to understand tumorigenesis and develop more targeted diagnostic and therapeutic strategies by exploiting the natural intercellular communication networks in tumors. In the context of oncology, regulatory therapy provides the possibility of reproducing the original conditions that are unfavorable for the existence of the cancer process and may thus be a feasible alternative to population treatments. We also review current access to the technology enabling regulatory intervention in the cancer process using exosomes. Full article

(This article belongs to the Special Issue Cancer Therapy: Where We Are and Where We Need to Go)

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21 pages, 855 KiB

Open AccessReview

The Microbiome Modulates the Immune System to Influence Cancer Therapy

by Ruchi Roy and Sunil Kumar Singh

Cancers 2024, 16(4), 779; https://doi.org/10.3390/cancers16040779 - 14 Feb 2024

Viewed by 1445

Abstract

The gut microbiota composition can affect the tumor microenvironment and its interaction with the immune system, thereby having implications for treatment predictions. This article reviews the studies available to better understand how the gut microbiome helps the immune system fight cancer. To describe this fact, different mechanisms and approaches utilizing probiotics to improve advancements in cancer treatment will be discussed. Moreover, not only calorie intake but also the variety and quality of diet can influence cancer patients’ immunotherapy treatment because dietary patterns can impair immunological activities either by stimulating or suppressing innate and adaptive immunity. Therefore, it is interesting and critical to understand gut microbiome composition as a biomarker to predict cancer immunotherapy outcomes and responses. Here, more emphasis will be given to the recent development in immunotherapies utilizing microbiota to improve cancer therapies, which is beneficial for cancer patients. Full article

(This article belongs to the Special Issue Cancer Therapy: Where We Are and Where We Need to Go)

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25 pages, 2736 KiB

Open AccessReview

MET in Non-Small-Cell Lung Cancer (NSCLC): Cross ‘a Long and Winding Road’ Looking for a Target

by Gianluca Spitaleri, Pamela Trillo Aliaga, Ilaria Attili, Ester Del Signore, Carla Corvaja, Chiara Corti, Jacopo Uliano, Antonio Passaro and Filippo de Marinis

Cancers 2023, 15(19), 4779; https://doi.org/10.3390/cancers15194779 - 28 Sep 2023

Cited by 3 | Viewed by 1832

Abstract

Non-Small-Cell Lung Cancer (NSCLC) can harbour different MET alterations, such as MET overexpression (MET OE), MET gene amplification (MET AMP), or MET gene mutations. Retrospective studies of surgical series of patients with MET-dysregulated NSCLC have shown worse clinical outcomes irrespective of the type of specific MET gene alteration. On the other hand, earlier attempts failed to identify the ‘druggable’ molecular gene driver until the discovery of MET exon 14 skipping mutations (METex14). METex14 are rare and amount to around 3% of all NSCLCs. Patients with METex14 NSCLC attain modest results when they are treated with immune checkpoint inhibitors (ICIs). New selective MET inhibitors (MET-Is) showed a long-lasting clinical benefit in patients with METex14 NSCLC and modest activity in patients with MET AMP NSCLC. Ongoing clinical trials are investigating new small molecule tyrosine kinase inhibitors, bispecific antibodies, or antibodies drug conjugate (ADCs). This review focuses on the prognostic role of MET, the summary of pivotal clinical trials of selective MET-Is with a focus on resistance mechanisms. The last section is addressed to future developments and challenges. Full article

(This article belongs to the Special Issue Cancer Therapy: Where We Are and Where We Need to Go)

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13 pages, 1331 KiB

Open AccessReview

Management of Gastro-Intestinal Toxicity of the Pi3 Kinase Inhibitor: Optimizing Future Dosing Strategies

by Claire Breal, Frederic Beuvon, Thibault de Witasse-Thezy, Solene Dermine, Patricia Franchi-Rezgui, Benedicte Deau-Fisher, Lise Willems, Eric Grignano, Adrien Contejean, Didier Bouscary, Jean Luc Faillie, Jean-Marc Treluyer, Corinne Guerin, Laurent Chouchana and Marguerite Vignon

Cancers 2023, 15(8), 2279; https://doi.org/10.3390/cancers15082279 - 13 Apr 2023

Viewed by 1299

Abstract

The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in cancer progression and in host immunity. Idelalisib was the first of this class to be approved with the second-generation Pi3 kinase inhibitors copanlisib, duvelisib and umbralisib, subsequently being approved in the United States. Real-world data are lacking, however, in relation to the incidence and toxicity of Pi3 kinase inhibitor-induced colitis. We here review, in the first instance, the general landscape of the Pi3K inhibitors in the context of hematological malignancies, with a focus on the adverse gastrointestinal side effects reported by various clinical trials. We further review the available worldwide pharmacovigilance data in relation to these drugs. Finally, we describe our own real-world experience with idelalisib-induced colitis management in our center and in a national setting. Full article

(This article belongs to the Special Issue Cancer Therapy: Where We Are and Where We Need to Go)

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