Insights into highly selective RET inhibitors in medullary thyroid cancer

Medullary thyroid cancer (MTC) is a neuroendocrine malignant tumor that originates from parafollicular C-cells, producing calcitonin. Approximately 75% of cases are sporadic, while the remaining 25% are hereditary. The main molecular alteration implicated in MTC tumorigenesis, whether sporadic or hereditary, is a point mutation in the RET gene. Surgery is the initial treatment of choice, while subsequent treatments are determined based on the tumor burden and rate of progression. While in case of single metastases, low tumor burden with slow rate of progression local treatments are recommended, systemic treatments are warranted in cases with large metastatic disease and rapidly progressive conditions. Beyond multikinase inhibitors (MKIs), new highly selective compounds against RET mutation, with high efficacy and good safety profile, have been recently used in clinical trials for advanced MTC patients.

This review focuses on the details of systemic treatments with highly selective RET inhibitors for advanced and metastatic MTC.