The approval of sotorasib (Lumakras) in 2021 to treat non-small cell lung cancer (NSCLC) harboring the KRAS-G12C mutation transformed KRAS from an undruggable oncogene to a druggable therapeutic target and created an overnight sensation in cancer research and therapy. Targeting KRAS mutations directly set the stage for research into effective treatments for about a quarter of all human cancers, but the excitement obscured a more sobering reality. Sotorasib and subsequent KRAS-targeting agents are the result of decades of painstaking basic and applied cancer research. Recent advances in immunotherapy and targeted therapy have significantly improved outcomes for many patients. However, these advances resulted in limited progress for those with RAS-mutated tumors, noted Dafna Bar-Sagi, PhD, Saul J. Farber Professor of Biochemistry and Molecular Pharmacology, Executive Vice President and Vice Dean for Science at NYU Langone Health. That scenario has changed dramatically with the emergence of therapeutics that target RAS directly and improvements in immune intervention technologies, she said.