Targeting Housekeeping To Tame Tumors

Targeting the cell housekeeping processes that cancer mutations hijack might be as effective at killing tumor cells as targeting the cancer-causing mutations themselves, a study suggests (Nature, DOI: 10.1038/nature10167). The cancer-fighting drug Gleevec targets a specific mutation, or oncogene, and effectively treats cancer patients who have the mutation. But Gleevec and similar genetically matched drugs help only a small percentage of patients. So some scientists are targeting normal cell processes that get co-opted by oncogenes in hopes of achieving Gleevec-like results. Stuart L. Sch reiber of the Broad Institute and Harvard University, Anna Mandinova and Sam W. Lee of Massachusetts General Hospital, and coworkers have found a molecule that selectively kills cancer cells and tumors in mice by blocking a housekeeping process: the ability to quench reactive oxygen species (ROS). That process is crucial for the survival of cancer cells, but not normal cells. The compound, piperlongumine, comes from the Indian long pepper plant. The team now plans to determine the specific cancer-causing mutations that make cancer cells reliant on ROS quenching, and thus vulnerable to piperlongumine, Schreiber says. Mandinova and Lee have started a company called Canthera Therapeutics to exploit the ROS strategy for cancer treatment.