Montero, JuanLetai, Antony2018-02-262018Montero, Joan, and Antony Letai. 2018. “Why do BCL-2 inhibitors work and where should we use them in the clinic?” Cell Death and Differentiation 25 (1): 56-64. doi:10.1038/cdd.2017.183. http://dx.doi.org/10.1038/cdd.2017.183.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34868855Intrinsic 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.en-USJournal Article2018-02-2610.1038/cdd.2017.183