Resistance Mechanisms to Anti-Epidermal Growth Factor Receptor Therapy in RAS/RAF Wild-Type Colorectal Cancer Vary by Regimen and Line of Therapy.
Christine M ParseghianRyan SunMelanie WoodsStefania NapolitanoHey Min LeeJumanah AlshenaifiJason A WillisShakayla NunezKanwal P S RaghavVan Karlyle MorrisJohn Paul ShenMadhulika EluriAlexey SorokinPreeti KanikarlaEduardo VilarMarko RehnAgnes AngTeresa TroianiEdmund S KopetzPublished in: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2022)
These findings support a model of resistance whereby transcriptomic mechanisms of resistance predominate in the presence of active cytotoxic chemotherapy combined with EGFRi, with a greater predominance of acquired MAPK mutations after single-agent EGFRi. The proposed model has implications for prospective studies evaluating EGFRi rechallenge strategies guided by acquired MAPK mutations, and highlights the need to address transcriptional mechanisms of resistance.