Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Frankfurt, Germany.
Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Frankfurt, Germany.
Biochim Biophys Acta Mol Cell Res. 2021 Apr;1868(5):118987. doi: 10.1016/j.bbamcr.2021.118987. Epub 2021 Feb 15.
The removal of cells by apoptosis is an essential process regulating tissue homeostasis. Cancer cells acquire the ability to circumvent apoptosis and survive in an unphysiological tissue context. Thereby, the Bcl-2 protein family plays a key role in the initiation of apoptosis, and overexpression of the anti-apoptotic Bcl-2 proteins is one of the molecular mechanisms protecting cancer cells from apoptosis. Recently, small molecules targeting the anti-apoptotic Bcl-2 family proteins have been identified, and with venetoclax the first of these BH3 mimetics has been approved for the treatment of leukemia. In solid tumors the anti-apoptotic Bcl-2 family proteins Mcl-1 and Bcl-xL are frequently overexpressed or genetically amplified. In this review, we summarize the role of Mcl-1 and Bcl-xL in solid tumors and compare the different BH3 mimetics targeting Mcl-1 or Bcl-xL.
细胞凋亡是调控组织内稳态的一个重要过程，细胞通过凋亡清除。癌细胞获得了逃避凋亡并在非生理组织环境中存活的能力。因此，Bcl-2 蛋白家族在凋亡的启动中起着关键作用，抗凋亡 Bcl-2 蛋白的过表达是保护癌细胞免受凋亡的分子机制之一。最近，已经鉴定出针对抗凋亡 Bcl-2 家族蛋白的小分子，并且 venetoclax 是第一个此类 BH3 模拟物，已被批准用于治疗白血病。在实体肿瘤中，抗凋亡 Bcl-2 家族蛋白 Mcl-1 和 Bcl-xL 经常过表达或基因扩增。在这篇综述中，我们总结了 Mcl-1 和 Bcl-xL 在实体肿瘤中的作用，并比较了针对 Mcl-1 或 Bcl-xL 的不同 BH3 模拟物。
