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Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis
Published on: February 16, 2015
Programs for cell death: apoptosis is only one way to go
1The David and Inez Myers Laboratory for Genetic Research, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract:
Cell death programs are major players in tissue homeostasis, development and cellular stress responses. A prominent cause of malignant transformation is the cumulative genetic alterations in pathways that regulate cellular growth and death. The processes that govern cell death following genotoxic stress are a major focus of basic research and are also very relevant to translational research in clinical oncology: understanding cell death following cancer therapy is essential for designing new treatment modalities. Cell death is usually, and sometimes automatically, linked with one of its major programs, apoptosis. Recent advances have led, however, to the emergence of additional, non-apoptotic cell death pathways, each with its triggers and readouts. Genotoxic stress appears to induce several cell death pathways, only part of which fall within the classical definition of apoptosis. Accordingly, solid tumor cells that are refractive to apoptosis were shown to die via non-apoptotic mechanisms. Recently we demonstrated that mitotic cell death induced by DNA damage in cells with defective G2/M checkpoint is mechanistically distinct from apoptosis. This review outlines recent advances in the understanding of molecular networks operative in apoptotic and non-apoptotic cell death mechanisms and their cross-talks.
Insights
Cell death, crucial for tissue health, involves apoptosis and other non-apoptotic pathways. Understanding these cell death mechanisms, especially after DNA damage, is vital for cancer therapy development.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Cell death programs are essential for tissue homeostasis, development, and stress responses.
- Genetic alterations in cell growth and death pathways contribute to malignant transformation.
- Understanding cell death post-genotoxic stress is critical for cancer therapy.
Purpose of the Study:
- To review recent advances in apoptotic and non-apoptotic cell death mechanisms.
- To explore the molecular networks and cross-talks involved in diverse cell death pathways.
- To highlight the relevance of non-apoptotic cell death in cancer therapy.
Main Methods:
- Literature review of recent advances in cell death research.
- Analysis of molecular mechanisms underlying apoptosis and non-apoptotic cell death.
- Discussion of genotoxic stress-induced cell death pathways.
Main Results:
- Genotoxic stress can induce multiple cell death pathways, including non-apoptotic mechanisms.
- Solid tumor cells resistant to apoptosis can die via alternative pathways.
- Mitotic cell death induced by DNA damage with checkpoint defects is distinct from apoptosis.
Conclusions:
- Cell death encompasses more than just apoptosis, with distinct non-apoptotic pathways playing significant roles.
- Non-apoptotic cell death mechanisms are crucial for understanding and overcoming cancer therapy resistance.
- Further research into the molecular intricacies of diverse cell death pathways is essential for advancing oncology.
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