Medullary thyroid carcinoma

To summarize recent developments in the diagnosis and management of patients with medullary thyroid cancer (MTC), with a focus on pathogenesis, systemic therapy, and future directions.

The addition of mutational analysis to cytological assessment of thyroid nodules has improved the diagnostic accuracy of MTC. The discovery of new genomic alterations and overexpression of certain factors allows for improved prognostication in MTC and provides potentially new therapeutic agents. New data suggest that tumor environment may be more immunogenic than previously thought in a subset of MTCs with identification of a new MTC-specific antigen leading to a revival of investigating immune-based therapy for this disease. The newly approved selective rearranged during transfection (RET0-inhibitors, selpercatinib and pralsetinib, offer promising results, and tolerability for patients with RET-mutated MTC; however, the development of resistance mechanisms may be problematic.

MTC has witnessed remarkable advancements in recent years. Our new understanding of some of the driver mutations in MTC allows for therapeutics with more tolerable adverse event profiles. However, there is still a need for more effective treatment strategies for subsets of patients without actionable mutations and for those who develop resistance to currently available therapies.