Modes of Regulated Cell Death in Cancer.

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. ©2021 American Association for Cancer Research.