The Problem of Apoptotic Processes Reversibility

Zakharov, I. I.; Savitskaya, M. A.; Онищенко, Г. Е.

doi:10.1134/s000629792010003x

Cited by 10 publications

(7 citation statements)

References 51 publications

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“…Anastasis appears to involve physiological healing processes, but unfortunately it facilitates cancer cell survival following therapeutic exposures. The potential challenges in the treatment of solid tumors associated with anastasis have been recently discussed [ 4 , 8 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Well Established and Yet Widely Overlooked Therapy-induced C...mentioning

confidence: 99%

“…We did PubMed searches to find research reports on this topic and noticed that the majority of recent publications (since 2019) on cancer cell response to therapeutic agents have not only overlooked anastasis but have also continued to use caspase activation, Annexin V staining, and/or positive TUNEL staining as markers of cancer cell death. Since 2019, however, there have been several comprehensive reviews on the potential dark side of anastasis in cancer therapy and how this response complicates the interpretation of results obtained by standard radiosensitivity and chemosensitivity assays in terms of cancer cell death (e.g., [ 4 , 8 , 25 , 26 , 27 , 28 ]).…”

Section: Well Established and Yet Widely Overlooked Therapy-induced C...mentioning

confidence: 99%

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What Are the Reasons for Continuing Failures in Cancer Therapy? Are Misleading/Inappropriate Preclinical Assays to Be Blamed? Might Some Modern Therapies Cause More Harm than Benefit?

Mirzayans

Murray

2022

IJMS

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Over 50 years of cancer research has resulted in the generation of massive amounts of information, but relatively little progress has been made in the treatment of patients with solid tumors, except for extending their survival for a few months at best. Here, we will briefly discuss some of the reasons for this failure, focusing on the limitations and sometimes misunderstanding of the clinical relevance of preclinical assays that are widely used to identify novel anticancer drugs and treatment strategies (e.g., “synthetic lethality”). These include colony formation, apoptosis (e.g., caspase-3 activation), immunoblotting, and high-content multiwell plate cell-based assays, as well as tumor growth studies in animal models. A major limitation is that such assays are rarely designed to recapitulate the tumor repopulating properties associated with therapy-induced cancer cell dormancy (durable proliferation arrest) reflecting, for example, premature senescence, polyploidy and/or multinucleation. Furthermore, pro-survival properties of apoptotic cancer cells through phoenix rising, failed apoptosis, and/or anastasis (return from the brink of death), as well as cancer immunoediting and the impact of therapeutic agents on interactions between cancer and immune cells are often overlooked in preclinical studies. A brief review of the history of cancer research makes one wonder if modern strategies for treating patients with solid tumors may sometimes cause more harm than benefit.

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Section: Well Established and Yet Widely Overlooked Therapy-induced C...mentioning

confidence: 99%

Section: Well Established and Yet Widely Overlooked Therapy-induced C...mentioning

confidence: 99%

What Are the Reasons for Continuing Failures in Cancer Therapy? Are Misleading/Inappropriate Preclinical Assays to Be Blamed? Might Some Modern Therapies Cause More Harm than Benefit?

Mirzayans

Murray

2022

IJMS

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“…Both Eph receptors and ephrin ligands are membrane-bound, thus eliciting a bidirectional signaling in the interacting pair of cells [248]. They constitute an intercellular communication mode with many functions, such as the formation of spatial boundaries during normal development [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. While they regulate processes such as proliferation, cell death, and invasion, it is their role in cell sorting and positioning that made their fame [249,250], for instance, in regulating the positioning of intestinal epithelial cells within the stem cell niche [244] and coordinating between intercellular communication, migration, and cell positioning [243].…”

Section: Trying To Fit Inmentioning

confidence: 99%

“…So, apart from initiatory and regulatory mechanisms, what exactly are these landmark morphological and biochemical events that define the essence of cell death? We know that cells can recover from apoptosis up to a certain point [4][5][6][7][8][9][10][11], and a name has been coined for that mechanism of recovery: anastasis, from the Greek "rising to life", also known as "resurrection" [5]. While saving cells from certain death is a desirable outcome in many situations, particularly in degenerative diseases, it might come at a highly dangerous price, as it allows cells which have acquired mutations to undergo oncogenic 2 of 32 transformation [12][13][14].…”

Section: Introduction: the Dead Cellmentioning

confidence: 99%

Cell Death, by Any Other Name…

Kandouz

2024

Cells

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Studies trying to understand cell death, this ultimate biological process, can be traced back to a century ago. Yet, unlike many other fashionable research interests, research on cell death is more alive than ever. New modes of cell death are discovered in specific contexts, as are new molecular pathways. But what is “cell death”, really? This question has not found a definitive answer yet. Nevertheless, part of the answer is irreversibility, whereby cells can no longer recover from stress or injury. Here, we identify the most distinctive features of different modes of cell death, focusing on the executive final stages. In addition to the final stages, these modes can differ in their triggering stimulus, thus referring to the initial stages. Within this framework, we use a few illustrative examples to examine how intercellular communication factors in the demise of cells. First, we discuss the interplay between cell–cell communication and cell death during a few steps in the early development of multicellular organisms. Next, we will discuss this interplay in a fully developed and functional tissue, the gut, which is among the most rapidly renewing tissues in the body and, therefore, makes extensive use of cell death. Furthermore, we will discuss how the balance between cell death and communication is modified during a pathological condition, i.e., colon tumorigenesis, and how it could shed light on resistance to cancer therapy. Finally, we briefly review data on the role of cell–cell communication modes in the propagation of cell death signals and how this has been considered as a potential therapeutic approach. Far from vainly trying to provide a comprehensive review, we launch an invitation to ponder over the significance of cell death diversity and how it provides multiple opportunities for the contribution of various modes of intercellular communication.

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“…During anastasis, the up-regulated TGFβ signaling and SNAI1 expression are thought to enhance EMT and chemotherapy resistance during tumor progression. Anastasis facilitates the transformation of tumor cells into cancer stem cells, potentially leading to increased resistance to drugs and tumor recurrence [ 120 , 127 ]. Xu et al observed that CD44, a stem cell marker, was highly expressed in anastatic breast cancer cells after induction of apoptosis by STS and paclitaxel.…”

Section: Anastasismentioning

confidence: 99%

Beyond Death: Unmasking the Intricacies of Apoptosis Escape

Ergün,

Aslan,

Demir

et al. 2024

Mol Diagn Ther

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The Problem of Apoptotic Processes Reversibility

Cited by 10 publications

References 51 publications

What Are the Reasons for Continuing Failures in Cancer Therapy? Are Misleading/Inappropriate Preclinical Assays to Be Blamed? Might Some Modern Therapies Cause More Harm than Benefit?

What Are the Reasons for Continuing Failures in Cancer Therapy? Are Misleading/Inappropriate Preclinical Assays to Be Blamed? Might Some Modern Therapies Cause More Harm than Benefit?

Cell Death, by Any Other Name…

Beyond Death: Unmasking the Intricacies of Apoptosis Escape

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