Deregulation of the bcl-2 oncogene underpins both the etiology and the chemoresistance of many significant tumors. The Bcl-2 protein mediates these effects by blocking physiological (programmed) cell death (apoptosis) of such malignant cells. In vitro models indicate that inhibitors of bcl-2 gene expression block this effect; however, no small molecule inhibitors of Bcl-2 protein expressed within them. The relative proliferation rates of these and other control cell lines will provide a conveniently quantifiable marker in any assay capable of screening combinatorial chemical libraries of great complexity for molecules blocking Bcl-2 function. Such species will have great potential and adjuncts to existing anti-cancer therapies, and may constitute novel chemotherapeutics in their own right.
Identification of bcl-2 inhibitors represents a rational approach to cancer chemotherapy with large commercial application.
