A yet more challenging resistance mechanism found in GIST lesions with KIT mutations as they progress clinically involves the transition from KIT to another novel oncogene, which shows strong resistant to these small molecular inhibitors due to the loss of KIT expression (Fletcher et al., 2003; Debiec-Rychter et al., 2005; Tu et al., 2018; Ou et al., 2019). The gene discussed is KIT; the disease is gastrointestinal stromal tumor.