Health & Environmental Research Online (HERO)


Print Feedback Export to File
7429646 
Journal Article 
Anti-apoptotic Bcl-2 
Frankel, SR; Chi, DowC; , 
2017 
Springer New York 
New York, NY 
Cancer Therapeutic Targets 
833-850 
The B-cell lymphoma/leukemia 2 (BCL-2) family represents a group of proteins involved in the regulation of the intrinsic (mitochondrial) apoptotic pathway. Approximately 25 members of the BCL-2 family have been grouped into three categories based on structure and function: (1) anti- apoptotic, (2) pro-apoptotic, and (3) BH3 only proteins. This chapter will focus on a family of five anti-apoptotic proteins: (1) BCL-2, (2) BCL-xL, (3) BCL-w, (4) MCL-1, and (5) A1. The decision for a cell to undergo apoptosis is regulated by the BCL-2 family of proteins. Inhibition of anti-apoptotic BCL-2 proteins is an active area of research and represents a novel pathway in cancer therapeutics. BH3 profiling is a functional assay that measures the degree to which a cancer cell is primed to undergo apoptosis by investigating how the cells evade apoptosis by three possible mechanisms: (1) inability of activator BH3-only proteins (Bim/Bid) to function, (2) loss of pro-apoptotic BCL-2 proteins (Bax/Bak), and (3) sequestration of activator BH3 proteins by anti-apoptotic BCL-2 proteins. Approaches to target BCL-2 include RNA antisense molecules (oblimersen, SPC2996); small-molecule inhibitors (venetoclax, obatoclax, ABT-737, navitoclax, AT-101); and stabilized alpha helix of BCL-2 (SAHB) peptides. These compounds are under various stages of clinical investigation in both solid and hematologic malignancies, both as single agents and in combination with other cytotoxic regimens