Diagnostics, Therapeutics and RET Inhibitor Resistance for RET Fusion–Positive Non-Small Cell Lung Cancers and Future Perspectives

Abstract 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.