Lessons learned from studying molecular mechanisms of resistance to ABL, EGFR, ALK, KIT, and RAF inhibitors in human cancers have highlighted the need for next-generation kinase inhibitors that are effective against acquired secondary resistance mutations (Demetri 2011; Roychowdhury and Talpaz 2011; Gainor and Shaw 2013; Lito et al. 2013; Van Allen et al. 2014; Hrustanovic et al. 2015). The gene discussed is ABL1; the disease is cancer.