Biomarkers of therapeutic response to BCL2 antagonists in cancer.

Cancer cells persist by resisting programmed cell death or apoptosis. In particular, an imbalance of proteins that regulate apoptosis leads to lack of response to apoptotic stimuli. Thus, restoring the ability of cancer cells to undergo apoptosis is highly desirable. One apoptosis pathway, the intrinsic pathway, involves perturbation of the mitochondria. The major players of this pathway are the members of the B cell CLL/lymphoma 2 (BCL2) family. Currently, three BCL2 antagonists are in clinical trials for cancer treatment. While these antagonists show various specificity and potency, the development of companion diagnostics is crucial for developing these compounds into viable cancer treatments. In this review we describe predictive and pharmacodynamic biomarkers for these agents. Future directions on biomarker development for this class of antagonist are also discussed.