Trends in targeting Bcl-2 anti-apoptotic proteins for cancer treatment

Apoptosis is the major mode of programmed cell death, which conduces to maintain tissue homeostasis, clearance of abnormal cells and development of organisms. Over the past two decades, great progress and significant clinical benefits in cancer treatment have been made by targeting Bcl-2 anti-apoptotic proteins. However, with the deep research of clinic, the therapeutic value of single target inhibitors is restricted due to the limited monotherapy activity, potential and complex drug resistance as well as monotherapy safety. This review focuses on recent advance in discovery of novel apoptosis inducers targeting Bcl-2 anti-apoptotic proteins aiming to overcome existing therapeutic limitations, and introduce the strategies and advanced technologies in the drug design and optimization.