Medullary thyroid cancer: therapeutic targets and molecular markers

The present review will provide an update of important studies in medullary thyroid cancer (MTC) with an emphasis on targeted preclinical and translational research studies published over the past 2 years.

Recent advances in the biology of MTC, particularly in RET proto-oncogene signaling, are now being translated into promising new therapies and biomarkers. Multifunction tyrosine kinase inhibitors that target RET, plus vascular endothelial growth factor receptors and additional kinases, are now being evaluated in Phase II clinical trials in MTC. Important unanswered questions include the optimal means for selecting high-risk patients, appropriate biomarkers for monitoring kinase inhibitor trials, and trial endpoints. Similar to ABL, epidermal growth factor receptors and other kinases, individual mutant RET forms have differential sensitivity to different inhibitors. In addition to RET, an old marker, calcitonin, has assumed increasing importance, but may not adequately reflect changes in tumor burden in RET inhibitor trials. A number of new therapeutic strategies are being developed that could be appropriate for the approximately 50% of patients who lack RET mutations in their tumors.

Progress is being made toward effective targeted MTC therapy. Patients with advanced, progressive MTC should be considered for enrollment in clinical trials.