Selective RET inhibitors is the current hot topic, making multikinase inhibitors a thing of the past. However, the limitation of various test approaches, coupled with lack of knowledge of acquired resistance mechanisms, and specific patient groups that bear special consideration, remains a challenge. Herein, we outline utility of various diagnostic techniques, provide evidence to guide management of RET-fusion-positive Non-Small Cell Lung Cancer (NSCLC) patients, including specific patient groups, such as EGFR-mutant NSCLC patients who acquired RET fusions after resisting EGFR TKIs, and offer a compendium of mechanisms of acquired resistance to RET targeted therapies. This review further provides a list of ongoing clinical trials and summarizes perspectives to guide future development of drugs and trials for this population.
Keywords: Acquired resistance; Molecular profiling; Multikinase inhibitor; Non-small cell lung cancer (NSCLC); RET fusion; Selective tyrosine kinase inhibitor.
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