Killing cancer cells by flipping the Bcl-2/Bax switch

Abstract

Impairment of apoptosis, the physiologic cell death process, is central to cancer development and renders tumors refractory to cytotoxic therapy. Bcl-2, the oncoprotein activated in follicular lymphoma, inhibits the conserved cell death pathway triggered by diverse cytotoxic agents, as do several close relatives. A small-molecule antagonist of these proteins has now been designed by Oltersdorf et al. Strikingly, ABT-737 sensitizes many tumors to cytotoxic agents and is effective as a single agent against certain lymphomas and solid tumors, provoking stable regression in some tumor xenografts. Hence, this work validates Bcl-2-like proteins as important new targets in cancer therapy.