Why do BCL-2 inhibitors work and where should we use them in the clinic?
Why do BCL-2 inhibitors work and where should we use them in the clinic?
复制标题
DOI：
10.1038/cdd.2017.183
复制
发表时间：
2018-01
影响因子：
12.4
通讯作者：
Letai A
中科院分区：
文献类型：
--
作者：
Montero J;Letai A
内源性细胞凋亡由BCL-2家族蛋白控制，但家族内相互作用的复杂性使得通过标准分子生物学技术预测细胞命运具有挑战性。我们讨论了BCL-2家族的调控以及如何确定细胞凋亡和抗凋亡依赖的准备。癌细胞通常采用抗凋亡防御机制来响应致癌应激或抗癌治疗。然而，通过确定它们的抗凋亡成瘾性，我们可以使用新的BH 3模拟物来压倒这种凋亡阻断。我们概述了这些独特的抗凋亡抑制剂的开发和使用，以及如何使用动态BH 3谱（DBP）将它们与其他抗癌药物联合收割机结合以改善个性化癌症治疗。
Intrinsic apoptosis is controlled by the BCL-2 family of proteins but the complexity of intra-family interactions makes it challenging to predict cell fate via standard molecular biology techniques. We discuss BCL-2 family regulation and how to determine cells’ readiness for apoptosis and anti-apoptotic dependence. Cancer cells often adopt anti-apoptotic defense mechanisms in response to oncogenic stress or anti-cancer therapy. However, by determining their anti-apoptotic addiction, we can use novel BH3 mimetics to overwhelm this apoptotic blockade. We outline the development and uses of these unique anti-apoptotic inhibitors and how to possibly combine them with other anti-cancer agents using dynamic BH3 profiling (DBP) to improve personalized cancer treatment.