Testing Ways to Trigger Cell Death From the Outside

Extract

Cells have two partially overlapping pathways that can induce programmed cell death. One of those branches is blocked by mutations in the p53 gene, which occur in more than half of tumors. So far scientists have been unable to find safe methods to activate the other branch.

That obstacle may be changing. Three drugs in early clinical trials are designed to activate “death receptors” on the cell's surface, the p53-independent pathway. The drugs—one small molecule and two monoclonal antibodies—appear relatively safe, and evidence from phase I and II trials suggests that the agents are active in a variety of tumor types.

“The proapoptotic death receptors represent a novel target for anticancer therapy,” said Roy S. Herbst, M.D. Ph.D., chief of thoracic medical oncology at the University of Texas M. D. Anderson Cancer Center, who led the phase I trial for one of the compounds. “From a clinician's point of view, and as someone who is interested in translational research, I think this is a huge thing because we have a new class of agents.”