Typified by selpercatinib in mutant RET tumors, a newer generation of superior inhibitors targeting mutant oncogenes are beginning to challenge long-held assumptions about the perceived mutual exclusivity of mitogenic drivers in lung cancer and beyond, uncovering co-existent mitogenic drivers whereby one ostensibly fitter sensitizing allele becomes dominant after which therapy reveals the other as a mechanism of escape. The gene discussed is RET; the disease is lung carcinoma.