Targeting RET in Medullary Thyroid Cancer

Vivek Subbiah, MD, discusses what sets medullary thyroid cancer apart from other thyroid histologies.

Vivek Subbiah, MD, an associate professor in the Investigational Cancer Therapeutics department, and medical director of the Clinical Center for Targeted Therapy, Cancer Medicine division at The University of Texas MD Anderson Cancer Center, discusses what sets medullary thyroid cancer (MTC) apart from other thyroid histologies.

Subbiah notes that the RET proto-oncogene encodes a transmembrane receptor tyrosine kinase which is activated by 2 mechanisms. These include mutations that involve the system glitch or kinase domains, and structural rearrangements which then allow for the fusion of RET to a prime partner.

In MTC, RET is activated by RET mutations which are more closely linked to aggressive disease. A large number of patients with metastatic MTC have these mutations and make up a great number of diagnosed cases.

Transcription:

0:08 | The RET proto-oncogene encodes a transmembrane receptor tyrosine kinase that is constantly activated by 2 distinct mechanisms. One is mutations involving the system glitch or kinase domains, and structural rearrangements that lead to fusion of RET to a prime partner. Collectively, these alterations result in ligand dependent signaling and oncogenesis.

0:33 | Specifically, for MTC, RET is activated by RET mutations. Overall, more than 60% of patients with metastatic MTC harbor that mutation and in germline patients who are also identified as multiple endocrine neoplasia [MEN] type 1/2, almost 100% have this lead mutation. The germline mutations result in hereditary MEN, type 2A, and type 2B. Collectively these hereditary cancer syndromes account for 25% of all diagnosed cases of MTC of the remaining 75% of sporadic MTC, and as I said, over 60% harbored the RET somatic mutations. RET mutations are associated with more aggressive disease in MTC, and thus, tumors in a majority of patients need a RET-targeted inhibitor.