Sotorasib and adagrasib, the first agents to directly target KRAS-mutated (mKRAS) cancers, became overnight sensations when they were approved in 2021 and 2022, respectively. But the race to stop mKRAS tumors is anything but a sprint. It began with the discovery of RAS in 1964, and the endgame remains elusive. “The first serious attempt to target KRAS came in 1984 and the race began to heat up in 1992 and 1993,” said Frank McCormick, PhD, Professor of Medicine at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco (UCSF), and leader of the National Cancer Institute RAS Initiative at Frederick National Laboratory. “By 2003, there were multiple clinical trials testing farnesyl transferases. All of these trials failed.”