Discovery, Development and Application of Innovative Approaches to Cancer Therapy

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

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 4022

Special Issue Editor

Special Issue Information

Dear Colleagues,

Immune checkpoint inhibitors (ICIs) are at the forefront in systemic therapy for various types of advanced cancer with impressive results. However, only a minority of cancer patients have benefited from this type of immunotherapy and several ICI clinical trials have failed to produce long-term clinical benefits. Therapeutic cancer vaccines have also failed to generate clinically significant outcomes in large phase III trials. The lack of robust clinically results, despite the ability of immunotherapies to prime and expand tumor antigen-specific T-cells, could at least be partially attributed to the inability of immunotherapy-induced T-cell antitumor responses to overcome immune escape mechanisms developed by the tumors. Such mechanisms attenuate the functional program and also limit the clonal expansion of tumor-reactive T-cells following the application of immunotherapies. Strategies aimed at modulating the evasion of tumors from immune surveillance have shown promising results that reform the therapeutic landscape of cancer. This Special Issue aims to focus on the discovery, development, and application of novel cellular and molecular approaches, applied as single therapeutic modalities or in combination, for the prevention and treatment of cancer. To this end, this Special Issue will accept manuscripts addressing translational cancer research, clinical research, and clinical studies on various topics including, but not limited to, immune checkpoint inhibitors , chimeric antigen receptor (CAR) T/NK-cell therapy and other cell therapies, vaccine-based therapies, combinatorial therapies, prognostic/predictive biomarkers, resistance mechanisms, microbiome and Immunotherapies, as well as novel targets of immunotherapies in the tumor microenvironment and in the periphery and management of therapy-induced toxicities.

Dr. Constantin N. Baxevanis
Guest Editor

Manuscript Submission Information

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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.

Keywords

  • immune checkpoint inhibitors
  • vaccines
  • cell therapies
  • CAR T/NK cells
  • immune resistance
  • immune surveillance
  • immunoediting
  • immunotherapy
  • targeted therapies
  • combinational therapeutic strategies
  • biomarkers

Published Papers (3 papers)

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Research

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17 pages, 4008 KiB  
Article
Α Humanized RANKL Transgenic Mouse Model of Progestin-Induced Mammary Carcinogenesis for Evaluation of Novel Therapeutics
Cancers 2023, 15(15), 4006; https://doi.org/10.3390/cancers15154006 - 07 Aug 2023
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Abstract
Receptor activator of nuclear factor-κB ligand (RANKL) is critically involved in mammary gland pathophysiology, while its pharmaceutical inhibition is being currently investigated in breast cancer. Herein, we investigated whether the overexpression of human RANKL in transgenic mice affects hormone-induced mammary carcinogenesis, and evaluated [...] Read more.
Receptor activator of nuclear factor-κB ligand (RANKL) is critically involved in mammary gland pathophysiology, while its pharmaceutical inhibition is being currently investigated in breast cancer. Herein, we investigated whether the overexpression of human RANKL in transgenic mice affects hormone-induced mammary carcinogenesis, and evaluated the efficacy of anti-RANKL treatments, such as OPG-Fc targeting both human and mouse RANKL or Denosumab against human RANKL. We established novel MPA/DMBA-driven mammary carcinogenesis models in TgRANKL mice that express both human and mouse RANKL, as well as in humanized humTgRANKL mice expressing only human RANKL, and compared them to MPA/DMBA-treated wild-type (WT) mice. Our results show that TgRANKL and WT mice have similar levels of susceptibility to mammary carcinogenesis, while OPG-Fc treatment restored mammary ductal density, and prevented ductal branching and the formation of neoplastic foci in both genotypes. humTgRANKL mice also developed MPA/DMBA-induced tumors with similar incidence and burden to those of WT and TgRANKL mice. The prophylactic treatment of humTgRANKL mice with Denosumab significantly prevented the rate of appearance of mammary tumors from 86.7% to 15.4% and the early stages of carcinogenesis, whereas therapeutic treatment did not lead to any significant attenuation of tumor incidence or tumor burden compared to control mice, suggesting the importance of RANKL primarily in the initial stages of tumorigenesis. Overall, we provide unique genetic tools for investigating the involvement of RANKL in breast carcinogenesis, and allow the preclinical evaluation of novel therapeutics that target hormone-related breast cancers. Full article
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Review

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26 pages, 1978 KiB  
Review
Is Immunotherapy Beneficial in Patients with Oncogene-Addicted Non-Small Cell Lung Cancers? A Narrative Review
Cancers 2024, 16(3), 527; https://doi.org/10.3390/cancers16030527 - 26 Jan 2024
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Abstract
Over the past 20 years, there has been a paradigm shift in the care of patients with non-small cell lung cancer (NSCLC), who now have a range of systemic treatment options including targeted therapy, chemotherapy, immunotherapy (ICI), and antibody–drug conjugates (ADCs). A proportion [...] Read more.
Over the past 20 years, there has been a paradigm shift in the care of patients with non-small cell lung cancer (NSCLC), who now have a range of systemic treatment options including targeted therapy, chemotherapy, immunotherapy (ICI), and antibody–drug conjugates (ADCs). A proportion of these cancers have single identifiable alterations in oncogenes that drive their proliferation and cancer progression, known as “oncogene-addiction”. These “driver alterations” are identified in approximately two thirds of patients with lung adenocarcinomas, via next generation sequencing or other orthogonal tests. It was noted in the early clinical development of ICIs that patients with oncogene-addicted NSCLC may have differential responses to ICI. The toxicity signal for patients with oncogene-addicted NSCLC when treated with ICIs also seemed to differ depending on the alteration present and the specific targeted agent used. Developing a greater understanding of the underlying reasons for these clinical observations has become an important area of research in NSCLC. In this review, we analyze the efficacy and safety of ICI according to specific mutations, and consider possible future directions to mitigate safety concerns and improve the outcomes for patients with oncogene-addicted NSCLC. Full article
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17 pages, 2908 KiB  
Review
Anti-Inflammatory and Immune Properties of Polyunsaturated Fatty Acids (PUFAs) and Their Impact on Colorectal Cancer (CRC) Prevention and Treatment
Cancers 2023, 15(17), 4294; https://doi.org/10.3390/cancers15174294 - 28 Aug 2023
Cited by 1 | Viewed by 1313
Abstract
Colorectal cancer (CRC) remains a leading cause of death from cancer worldwide, with increasing incidence in the Western world. Diet has become the focus of research as a significant risk factor for CRC occurrence, and the role of dietary polyunsaturated fatty acids (PUFAs) [...] Read more.
Colorectal cancer (CRC) remains a leading cause of death from cancer worldwide, with increasing incidence in the Western world. Diet has become the focus of research as a significant risk factor for CRC occurrence, and the role of dietary polyunsaturated fatty acids (PUFAs) has become an area of interest given their potential role in modulating inflammation, particularly in the pro-carcinogenic inflammatory environment of the colon. This work reviews the main types of PUFAs, their characteristics, structure, and physiologic role. We then highlight their potential role in preventing CRC, their signaling function vis-à-vis tumorigenic signaling, and their subsequent potential role in modulating response to different treatment modalities. We review pre-clinical and clinical data and discuss their potential use as adjunct therapies to currently existing treatment modalities. Given our understanding of PUFAs’ immune and inflammation modulatory effects, we explore the possible combination of PUFAs with immune checkpoint inhibitors and other targeted therapies. Full article
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