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Interplay between Cell Death and Cell Proliferation Reveals New Strategies for Cancer Therapy

Journal

Publisher

MDPI
DOI: 10.3390/ijms23094723

Keywords

cell death; cancer resistance; apoptosis; immunogenic cell death; chemotherapy; cancer cell life-cycle

Funding

  1. US Department of Defense [CDMRP/PCRP 367 (W81XWH-20-10353)]
  2. Patrick C. Walsh Prostate Cancer Research Fund
  3. Prostate Cancer Foundation
  4. NCI [54CA143803, CA163124, CA093900, CA143055]
  5. William and Carolyn Stutt Research Fund
  6. Ronald Rose
  7. MC Dean, Inc.
  8. William and Marjorie Springer
  9. Mary and Dave Stevens
  10. Louis Dorfman
  11. Jones Family Foundation

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Cell division and cell death are essential processes in growth and development. Cancer is caused by abnormal regulation of these processes, and traditional anti-cancer treatments trigger apoptosis, to which cancer cells are resistant. Understanding how drugs kill cancer cells is crucial for developing more effective treatments. Cell cycle-independent forms of cell death, such as necroptosis or ferroptosis, have potential immunogenic effects, providing alternative strategies against tumors.
Cell division and cell death are fundamental processes governing growth and development across the tree of life. This relationship represents an evolutionary link between cell cycle and cell death programs that is present in all cells. Cancer is characterized by aberrant regulation of both, leading to unchecked proliferation and replicative immortality. Conventional anti-cancer therapeutic strategies take advantage of the proliferative dependency of cancer yet, in doing so, are triggering apoptosis, a death pathway to which cancer is inherently resistant. A thorough understanding of how therapeutics kill cancer cells is needed to develop novel, more durable treatment strategies. While cancer evolves cell-intrinsic resistance to physiological cell death pathways, there are opportunities for cell cycle agnostic forms of cell death, for example, necroptosis or ferroptosis. Furthermore, cell cycle independent death programs are immunogenic, potentially licensing host immunity for additional antitumor activity. Identifying cell cycle independent vulnerabilities of cancer is critical for developing alternative strategies that can overcome therapeutic resistance.

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