BCL2 Inhibitors: Insights into Resistance

Abstract

Over the last decade, improved understanding of the mechanisms and structures of proteins integral to apoptosis have enabled therapeutic targeting of BCL2 to become more specific, less toxic and ultimately more clinically effective. The first BCL2-selective inhibitor, venetoclax, is now approved for use in patients with relapsed and refractory chronic lymphocytic leukemia (CLL) in multiple countries. Early phase clinical trials demonstrated an 80% overall response rates in patients with relapsed/refractory CLL, independent of traditional risk factors, without undue toxicity. Venetoclax is also highly active in other lymphoid malignancies that express high levels of its target, BCL2, such as ..