However, as with other clinical trials involving targeted therapies, such as the MEK inhibitors in KRAS-mutant NSCLC patients [127–133] and the BRAF inhibitors in BRAFV600E mutant colorectal cancer patients [134–136], adaptive resistance to single-agent therapy with adagrasib and sotorasib eventually occurred in most patients. The gene discussed is KRAS; the disease is colorectal cancer.