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Modes of Regulated Cell Death in Cancer

Elle Koren and Yaron Fuchs
Elle Koren
Laboratory of Stem Cell Biology and Regenerative Medicine, Department of Biology, Technion Israel Institute of Technology, Haifa, Israel. Lorry Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion Israel Institute of Technology, Haifa, Israel.
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Yaron Fuchs
Laboratory of Stem Cell Biology and Regenerative Medicine, Department of Biology, Technion Israel Institute of Technology, Haifa, Israel. Lorry Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion Israel Institute of Technology, Haifa, Israel.
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  • For correspondence: yfuchs@technion.ac.il
DOI: 10.1158/2159-8290.CD-20-0789 Published February 2021
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Abstract

Cell suicide pathways, termed regulated cell death (RCD), play a critical role in organismal development, homeostasis, and pathogenesis. Here, we provide an overview of key RCD modalities, namely apoptosis, entosis, necroptosis, pyroptosis, and ferroptosis. We explore how various RCD modules serve as a defense mechanism against the emergence of cancer as well as the manner in which they can be exploited to drive oncogenesis. Furthermore, we outline current therapeutic agents that activate RCD and consider novel RCD-based strategies for tumor elimination.

Significance: A variety of antitumor therapeutics eliminate cancer cells by harnessing the devastating potential of cellular suicide pathways, emphasizing the critical importance of RCD in battling cancer. This review supplies a mechanistic perspective of distinct RCD modalities and explores the important role they play in tumorigenesis. We discuss how RCD modules serve as a double-edged sword as well as novel approaches aimed at selectively manipulating RCD for tumor eradication.

Footnotes

  • Cancer Discov 2021;11:245–65

  • Received June 4, 2020.
  • Revision received September 15, 2020.
  • Accepted October 29, 2020.
  • Published first January 18, 2021.
  • ©2021 American Association for Cancer Research.
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Cancer Discovery: 11 (2)
February 2021
Volume 11, Issue 2
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Modes of Regulated Cell Death in Cancer
Elle Koren and Yaron Fuchs
Cancer Discov February 1 2021 (11) (2) 245-265; DOI: 10.1158/2159-8290.CD-20-0789

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Modes of Regulated Cell Death in Cancer
Elle Koren and Yaron Fuchs
Cancer Discov February 1 2021 (11) (2) 245-265; DOI: 10.1158/2159-8290.CD-20-0789
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    • Abstract
    • Introduction
    • Overview of the Core Mechanisms of RCD
    • RCD as a Defense Mechanism against Cancer
    • Hijacking RCD to Drive Tumorigenesis
    • Novel Approaches to Target RCD pathways in Cancer
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