Sanofi, Merck, others race to restore stymied kill switch in cancer

Cancer researchers have been rethinking the way new drugs are developed as investigations of new medicines focus more on molecular targets than on the organs where tumors originate. And this evolution in clinical development has crossed paths with the race to advance drugs that restore function of a protein to send cancer cells to their grave.

At the intersection are pharma companies such as Merck ($MRK), Roche ($RHHBY) and Sanofi ($SNY) and smaller players such as Cellceutix seeking breakthroughs.

They have probed the role of the p53 protein in the death of cells with damaged DNA, and how cancer cells have found a variety of ways to stymie p53 function to stay alive and multiply. Yet pharma outfits have long hunted for drugs to revive the activity of the protein without much to show for their labors in human cancers.

Over the weekend The New York Times highlighted the progress of the three drug giants in the race to advance drugs that impact p53, which is incapacitated in a variety of common and rare cancers. Sanofi is advancing one of its compounds in a trial focused on patients with a rare fat-cell cancer known as liposarcoma, but the ubiquity of p53 inactivation across tumor types opens the door to testing individual drugs against cancers in many different organs at the same time. 

"This is a taste of the future in cancer drug development," said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society, in the Times article. "I expect the organ from which the cancer came from will be less important in the future and the molecular target more important."

Of course, behind many hot targets in cancer research are compelling stories of wiping out tumors, with the most compelling successes often found in mice, unfortunately. Cancer cells conspire in a variety of ways, including attachment of double minute 2 proteins to p53, to silence the kill switch.

Roche has already fallen short with compounds known as Nutlins (named after its Nutley, NJ, lab) that were designed to free p53 from the clutches of the double-minute protein. Tantalizing discoveries in the lab aren't often easy to translate into useful drugs. But Roche and others haven't given up on this target.

- check out The New York Times article (sub. req.)