10 distinct alterations in KRAS, NRAS, BRAF, and MEK were identified in a KRASG12C NSCLC patient with acquired resistance to Adagrasib.483 In another clinical study, more than one potential resistance mechanism was identified in 41% (7/17) of patients with KRASG12C NSCLC or CRC.289 As such, the heterogeneity of resistance mechanisms poses challenges to both basic research and clinical treatments. The gene discussed is BRAF; the disease is non-small cell lung carcinoma.