摘要
Regulated cell death(RCD),also well-known as programmed cell death(PCD),refers to the form of cell death that can be regulated by a variety of biomacromolecules,which is distinctive from accidental cell death(ACD).Accumulating evidence has revealed that RCD subroutines are the key features of tumorigenesis,which may ultimately lead to the establishment of different potential therapeutic strategies.Hitherto,targeting the subroutines of RCD with pharmacological small-molecule compounds has been emerging as a promising therapeutic avenue,which has rapidly progressed in many types of human cancers.Thus,in this review,we focus on summarizing not only the key apoptotic and autophagy-dependent cell death signaling pathways,but the crucial pathways of other RCD subroutines,including necroptosis,pyroptosis,ferroptosis,parthanatos,entosis,NETosis and lysosomedependent cell death(LCD)in cancer.Moreover,we further discuss the current situation of several small-molecule compounds targeting the different RCD subroutines to improve cancer treatment,such as single-target,dual or multiple-target small-molecule compounds,drug combinations,and some new emerging therapeutic strategies that would together shed new light on future directions to attack cancer cell vulnerabilities with small-molecule drugs targeting RCD for therapeutic purposes.
基金
The study was supported by the Fundamental Research Funds for the National Natural Science Foundation of China(82003879,81773889,82073998)
Science and Technology Department of Sichuan Province(2022JDRC0045)
Central Universities(YJ201880)
Youth Talent Promotion Project of China Association for Science and Technology(CACM-2020 QNRC1-01)
1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21061).Parts of images generated from BioRender.com.
