While the responses documented are unprecedented for patients with mCRCBRAF-V600E, these still compare unfavorably with the higher response rates observed in BRAF-mutant metastatic melanomas treated with anti-BRAF therapy9,10 and display a high degree of heterogeneity, which underscores the need for a deeper understanding of factors modulating treatment response that can optimize the clinical management of patients1,21. Here, BRAF is linked to metastatic melanoma.