Genentech's Avi Ashkenazi suspects that using ligands to bind to decoy receptors present in healthy cells, but not in cancer cells, could trigger apoptosis in tumors. Scientists studying signal transduction have spent the past several years piecing together the cell's apoptotic machinery-the complex signaling mechanisms that tell damaged cells to commit suicide. The discovery of more signaling proteins and their receptors has given biotechnology companies potential tools to fix this machinery when it goes awry. The investment community has followed this search for drugs with interest because successful apoptotic agents could treat diseases like cancer with more specificity and fewer side effects.
Tumor cells proliferate when that engine fails to operate.
Potential methods of repair include finding chemicals that target receptors to restore the apoptotic function in tumor cells, inducing apoptosis in a tumor's developing blood vessel, and imitating apoptosis through the introduction of engineered bacteria. Avi Ashkenazi, senior scientist in the department of molecular oncology at South San Francisco, Calif.-based Genentech Inc., is targeting receptors. He notes that the apoptotic engine is present in cancer cells but has a faulty starter switch. In vitro experiments have demonstrated how this process might work. Because cancer cells lack the apoptotic brakes that the decoy receptors provide healthy cells, the ligand binds directly to the death-inducing receptors, selectively initiating apoptosis in the cancer tissues.