Locking up Bcl

While the Bcl-2 family of proteins has long been recognized as promising cancer targets because of their role in regulating apoptosis, they have historically been considered undruggable with conventional small molecule chemistries. But they remain attractive targets, because they would address general mechanisms of cancer cell survival.

Bcl-2 and Bcl-xL are up-regulated in a number of cancers, particularly in the face of chemotherapy. The paradigmatic case is follicular lymphoma, where a chromosomal translocation results in the Bcl-2 gene coming under the regulation of an Ig promoter that is constitutively on. As a result, Bcl-2 is cranked up all the time, and the cell needs it to live. ...