The rationalization of cancer therapy
Alan Ashworth and Christopher Lord are known for the ingenious application of poly(ADP-ribose) inhibitors to the treatment of BRCA-mutant tumors, an approach that migrated from laboratory bench to phase II clinical trials in less than five years. This work, an application of the synthetic lethal principle borrowed from genetic analysis and applied to tumor therapy, is described in their review, which traces the evolution of anti-cancer drugs from the cytotoxic blunt instruments that remain the principal weapons against cancer to date, through the more refined and sophisticated drugs - notably herceptin and imatinib - targeted at molecules known to be modified in specific tumors, and finally describes how an understanding of the workings of cells as a whole, and the entire panoply of changes that characterize a tumor cell, and not just a single mutant molecule, will become the basis of drug treatment.