In a case series of 20 RAS-BRAF wt patients showing progression after anti-EGFR mAbs treatment, NGS analysis revealed that RAS mutations and HER2/MET amplifications were the most frequently detected resistance mechanisms in both tissue and plasma samples, the authors demonstrating the involvement of both intralesion and interlesion tumor heterogeneity in the emergence of the complex resistance mechanisms [108]. The gene discussed is BRAF; the disease is neoplasm.