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The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by gene fusion in 1%-2% of non-small cell lung cancers (NSCLC) and rarely in other cancer types. Selpercatinib is a highly selective RET kinase inhibitor that has recently been approved by the FDA in lung and thyroid cancers with activating RET gene fusions and mutations. Molecular mechanisms of acquired resistance to selpercatinib are poorly understood.

clinical cancer research

Overcoming MET-Dependent Resistance to Selective RET Inhibition in Patients with RET Fusion–Positive Lung Cancer by Combining Selpercatinib with Crizotinib