Our discovery that BRCA2 mutations identify patients susceptible to the action of TRAIL agonists suggests that TRAIL could be used in these patients in analogy to the way the recognition of the relevance of microsatellite instability (MSI) preceded the success of checkpoint inhibitors (CPI) in treating MSI-high colorectal cancer patients after the failure of CPI in unselected cohorts [25,63,64,65]. The gene discussed is BRCA2; the disease is colorectal cancer.