Resistance Mechanisms to Anti–Epidermal Growth Factor Receptor Therapy in <i>RAS/RAF</i> Wild-Type Colorectal Cancer Vary by Regimen and Line of Therapy

Abstract

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.