Cell Death and Survival Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria 3084, Australia.
Cell Death and Survival Laboratory, School of Cancer Medicine, La Trobe University, Bundoora, Victoria 3086, Australia.
Biochem Soc Trans. 2021 Nov 1;49(5):2397-2410. doi: 10.1042/BST20210750.
The deregulation of apoptosis is a key contributor to tumourigenesis as it can lead to the unwanted survival of rogue cells. Drugs known as the BH3-mimetics targeting the pro-survival members of the BCL-2 protein family to induce apoptosis in cancer cells have achieved clinical success for the treatment of haematological malignancies. However, despite our increasing knowledge of the pro-survival factors mediating the unwanted survival of solid tumour cells, and our growing BH3-mimetics armamentarium, the application of BH3-mimetic therapy in solid cancers has not reached its full potential. This is mainly attributed to the need to identify clinically safe, yet effective, combination strategies to target the multiple pro-survival proteins that typically mediate the survival of solid tumours. In this review, we discuss current and exciting new developments in the field that has the potential to unleash the full power of BH3-mimetic therapy to treat currently recalcitrant solid malignancies.
细胞凋亡失调是肿瘤发生的一个关键因素，因为它会导致流氓细胞不受控制地存活。被称为 BH3 模拟物的药物靶向 BCL-2 蛋白家族的生存成员，以诱导癌细胞凋亡，在治疗血液恶性肿瘤方面取得了临床成功。然而，尽管我们对介导实体瘤细胞不受控制存活的生存因子有了越来越多的了解，并且我们的 BH3 模拟物武器库也在不断增加，但 BH3 模拟物治疗在实体瘤中的应用尚未发挥其全部潜力。这主要归因于需要确定临床上安全但有效的联合策略，以针对通常介导实体瘤存活的多种生存蛋白。在这篇综述中，我们讨论了该领域的当前和令人兴奋的新进展，这些进展有可能释放 BH3 模拟物治疗的全部潜力，以治疗目前难以治疗的实体恶性肿瘤。
