Advances in Targeting RET-Dependent Cancers

Abstract RET alterations have been characterized as oncogenic drivers in multiple cancers. The clinical validation of highly selective RET inhibitors demonstrates the utility of specific targeting of aberrantly activated RET in patients with cancers such as medullary thyroid cancer or non–small cell lung cancer. The remarkable responses observed have opened the field of RET-targeted inhibitors. In this review, we seek to focus on the impact of therapeutic RET targeting in cancers. Significance: Successful clinical translation of selective RET inhibitors is poised to alter the therapeutic landscape of altered cancers. Questions that clearly need to be addressed relate to the ability to maintain long-term inhibition of tumor cell growth, how to prepare for the potential mechanisms of acquired resistance, and the development of next-generation selective RET inhibitors.