Killarney Shane T, Tait Stephen W G, Green Douglas R, Wood Kris C
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
Cancer Research UK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK.
Trends Cell Biol. 2024 Mar;34(3):225-238. doi: 10.1016/j.tcb.2023.07.005. Epub 2023 Aug 10.
Cytotoxic chemo-, radio-, and targeted therapies frequently elicit apoptotic cancer cell death. Mitochondrial outer membrane permeabilization (MOMP) is a critical, regulated step in this apoptotic pathway. The residual cancer cells that survive treatment serve as the seeds of eventual relapse and are often functionally characterized by their transient tolerance of multiple therapeutic treatments. New studies suggest that, in these cells, a sublethal degree of MOMP, reflective of incomplete apoptotic commitment, is widely observed. Here, we review recent evidence that this sublethal MOMP drives the aggressive features of residual cancer cells while templating a host of unique vulnerabilities, highlighting how failed apoptosis may counterintuitively enable new therapeutic strategies to target residual disease (RD).
细胞毒性化疗、放疗和靶向治疗常常引发癌细胞凋亡性死亡。线粒体外膜通透性改变（MOMP）是这一凋亡途径中的一个关键且受调控的步骤。经治疗后存活下来的残留癌细胞是最终复发的根源，其功能特征通常表现为对多种治疗具有短暂耐受性。新的研究表明，在这些细胞中，广泛观察到一种亚致死程度的MOMP，这反映了不完全的凋亡进程。在此，我们综述近期的证据，即这种亚致死性MOMP驱动残留癌细胞的侵袭性特征，同时形成一系列独特的脆弱性，突出了凋亡失败可能会以违反直觉的方式促成针对残留疾病（RD）的新治疗策略。
