We identified trametinib sensitizing variants as causing loss-of-function in EGFR (Fig. 2a, z-score < −2; Methods), indicating that combination therapies targeting RAF-MEK and EGFR are effective in BRAF-mutant colorectal cancer (CRC), and consistent with the clinical approval EGFR and BRAF inhibitors in CRC30–32. Here, BRAF is linked to colorectal cancer.