After decades of trying, in 2013 scientists developed a breakthrough drug that targets one of the most hard-to-hit cancer-related proteins, called KRAS. Now results on the first KRAS inhibitor to enter a clinical trial have been released and, so far, look promising. The experimental drug, AMG 510, specifically targets a mutated form of KRAS called G12C. About a third of all cancers are driven by harmful mutations in the RAS family of genes. The KRAS G12C mutation is found in approximately 13% of people with lung cancer, 3% of those with colorectal cancer, and 1% to 3% of people with other solid tumors. That translates to tens of thousands of people diagnosed with cancer each year, said one of the trial’s investigators, Greg Durm, M.D., of the Indiana University School of Medicine. In mouse models of human cancer, the treatment completely shrank tumors and, in some cases, led to long-lasting cures. And, based on preliminary data from a small number of patients, AMG 510 appeared to be safe and to have activity against different types of tumors with a KRAS G12C mutation. Mutant KRAS proteins were once considered “undruggable” because conventional approaches to blocking enzymes wouldn’t work for KRAS. That view recently began to change as advances in technology and drug discovery techniques revealed a new way to target the protein. Early results from the clinical trial, published October 30 in Nature, are “extremely exciting,” Dr. Durm said. KRAS is “something we’ve been working to target for decades, and we finally have something that looks not only tolerable, but also effective,” he added. The percentage of patients whose cancer shrank or disappeared after AMG 510 treatment was “very high for a new drug, and that’s why everyone is so excited about it,” said another of the trial’s investigators, Gerald Falchook, M.D., of Sarah Cannon Research Institute in Denver, Colorado.