Receptor tyrosine kinase fusion-mediated resistance to EGFR-TKI in EGFR-mutant NSCLC: a multi-center analysis and literature review

Drug resistance remains a significant challenge in EGFR-mutant NSCLC tumors engage due to pathway reactivation, pathway bypass and pathway indifference resistance mechanisms to evade tyrosine kinase inhibitor (TKI) suppression. Fusion of receptor tyrosine kinases (RTKs), such as RET, ALK, and FGFR3, has been reported to mediate EGFR TKI resistance. Given the rarity of these fusions and heterogenous nature of the condition, no prospective clinical trials evaluated the incidence, safety, and therapeutic benefit of dual EGFR-RTK inhibition.