BCL-2: found bound and drugged!

The BCL-2 gene was first cloned in 1985 from the t(14;18) chromosomal translocation found in nearly all follicular lymphomas. BCL-2 is understood to have a central role in inhibiting apoptosis. Now, Oltersdorf et al. report the development of a high-affinity, mechanistically validated small-molecule antagonist of BCL-2 that kills cancer in mouse xenograft models and primary human cancer cells in vitro. The two decades spanning these two achievements provide an interesting case study of rational drug development. The investigation of antiapoptotic protein antagonists holds new promise for selectively inducing programmed cell death in cancer cells.