Special Issue "The Bright and Dark Sides of Apoptosis and Other Modes of Cell “Death” in Cancer Therapy"

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

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editor

Prof. Dr. Razmik Mirzayans
E-Mail Website
Guest Editor

Special Issue Information

Dear Colleagues,

Stress-induced programmed cell death (e.g., through apoptosis) and “functional death” (e.g., dormancy through premature senescence) in cancer cells have long been regarded as favorable outcomes in cancer therapy. In the past decade, however, it has become evident that while these responses are essential for initial tumor control, they can also contribute to disease relapse, at least in solid tumors. Apoptotic cancer cells, for example, not only secrete tumor-promoting factors but can also undergo a reversal process (through anastasis), giving rise to tumor repopulating progeny. Reversal of a subset of apoptotic/dormant cancer cells contributes to intratumor heterogeneity, which poses a major challenge in treating cancer patients with metastatic disease. Unfortunately, intratumor heterogeneity is overlooked in most preclinical methods used in anticancer studies.

The purpose of this Special Issue is to provide a comprehensive update on molecular events that underlie intratumor heterogeneity in the context of cancer therapy. Reviews and original articles addressing the dark side of stress-induced apoptosis and senescence in solid tumors are particularly welcomed.

Prof. Dr. Razmik Mirzayans
Guest Editor

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 papers will be 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 2200 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

  • intratumor heterogeneity
  • single-cell analysis
  • senescence
  • senotherapeutics
  • apoptosis and tumorigenicity
  • anastasis
  • cell fusion
  • novel therapeutic strategies targeting dormant cancer cells

Published Papers (3 papers)

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Research

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Communication
Profiling Anti-Apoptotic BCL-xL Protein Expression in Glioblastoma Tumorspheres
Cancers 2020, 12(10), 2853; https://doi.org/10.3390/cancers12102853 - 02 Oct 2020
Cited by 2 | Viewed by 927
Abstract
Glioblastoma (GBM) is one of the cancers with the worst prognosis, despite huge efforts to understand its unusual heterogeneity and aggressiveness. This is mainly due to glioblastoma stem cells (GSCs), which are also responsible for the frequent tumor recurrence following surgery, chemotherapy or [...] Read more.
Glioblastoma (GBM) is one of the cancers with the worst prognosis, despite huge efforts to understand its unusual heterogeneity and aggressiveness. This is mainly due to glioblastoma stem cells (GSCs), which are also responsible for the frequent tumor recurrence following surgery, chemotherapy or radiotherapy. In this study, we investigate the expression pattern of the anti-apoptotic BCL-xL protein in several GBM cell lines and the role it might play in GSC-enriched tumorspheres. We report that several GBM cell lines have an increased BCL-xL expression in tumorspheres compared to differentiated cells. Moreover, by artificially modulating BCL-xL expression, we unravel a correlation between BCL-xL and tumorsphere size. In addition, BCL-xL upregulation appears to sensitize GBM tumorspheres to newly developed BH3 mimetics, opening promising therapeutic perspectives for treating GBM patients. Full article
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Review

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Review
Anastasis: Return Journey from Cell Death
Cancers 2021, 13(15), 3671; https://doi.org/10.3390/cancers13153671 - 22 Jul 2021
Viewed by 274
Abstract
For over 20 years, it has been a dogma that once the integrity of mitochondria is disrupted and proapoptotic proteins that are normally located in the intermembrane space of mitochondria appeared in the cytoplasm, the process of cell death becomes inevitable. However, it [...] Read more.
For over 20 years, it has been a dogma that once the integrity of mitochondria is disrupted and proapoptotic proteins that are normally located in the intermembrane space of mitochondria appeared in the cytoplasm, the process of cell death becomes inevitable. However, it has been recently shown that upon removal of the death signal, even at the stage of disturbance in the mitochondria, cells can recover and continue to grow. This phenomenon was named anastasis. Here, we will critically discuss the present knowledge concerning the mechanisms of cell death reversal, or development of anastasis, methods for its detection, and what role signaling from different intracellular compartments plays in anastasis stimulation. Full article
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Review
Senescent Tumor CD8+ T Cells: Mechanisms of Induction and Challenges to Immunotherapy
Cancers 2020, 12(10), 2828; https://doi.org/10.3390/cancers12102828 - 30 Sep 2020
Cited by 2 | Viewed by 732
Abstract
The inability of tumor-infiltrating T lymphocytes to eradicate tumor cells within the tumor microenvironment (TME) is a major obstacle to successful immunotherapeutic treatments. Understanding the immunosuppressive mechanisms within the TME is paramount to overcoming these obstacles. T cell senescence is a critical dysfunctional [...] Read more.
The inability of tumor-infiltrating T lymphocytes to eradicate tumor cells within the tumor microenvironment (TME) is a major obstacle to successful immunotherapeutic treatments. Understanding the immunosuppressive mechanisms within the TME is paramount to overcoming these obstacles. T cell senescence is a critical dysfunctional state present in the TME that differs from T cell exhaustion currently targeted by many immunotherapies. This review focuses on the physiological, molecular, metabolic and cellular processes that drive CD8+ T cell senescence. Evidence showing that senescent T cells hinder immunotherapies is discussed, as are therapeutic options to reverse T cell senescence. Full article
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