New Prospect For Tackling Cancer

A nucleotide analog that interferes with protein degradation halts tumor growth in a new way and may become a new cancer treatment, according to a report in Nature (2009, 458, 732). Damaged or unnecessary proteins throughout the body get marked for destruction with small protein tags and are degraded by an enzyme called the proteasome. A drug that blocks the proteasome has proven effective at treating some types of blood cancer, so researchers are interested in targeting other parts of the pathway with an eye toward developing complementary cancer drugs. Now, a team at Millennium Pharmaceuticals has developed MLN4924, a small molecule that resembles the nucleotide adenosine 5′-monophosphate and blocks activation of a small protein tag called NEDD8, which switches on an enzyme upstream of the proteasome. MLN4924 stops tumor growth in mice and is in early-stage clinical trials for several types of cancer. It might not become a drug, but it will nonetheless be a great tool for learning more about protein degradation, says Caltech biochemist Raymond J. Deshaies in a commentary accompanying the report.