In vitro genetic screening and functional investigations identified that dual blockade of EGFR and MEK prevents acquired resistance, and Misale et al. performed experiments in vivo using PDXs derived from a CRC patient carrying a quadruple wild-type gene profile (BRAF, KRAS, NRAS, and PIK3CA), which recapitulates the expression profile of patients sensitive to anti-EGFR antibodies. The gene discussed is EGFR; the disease is colorectal carcinoma.