Personalized Medicine in Medullary Thyroid Carcinoma: A Broad Review of Emerging Treatments

Abstract

Medullary thyroid carcinoma (MTC) arises from parafollicular cells in the thyroid gland, and although rare, it represents an aggressive type of thyroid cancer. MTC is recognized for its low mutational burden, with point mutations in RET or RAS genes being the most common oncogenic events. MTC can be resistant to cytotoxic chemotherapy, and multitarget kinase inhibitors (MKIs) have been considered a treatment option. They act by inhibiting the activities of specific tyrosine kinase receptors involved in tumor growth and angiogenesis. Several tyrosine kinase inhibitors are approved in the treatment of advanced MTC, including vandetanib and cabozantinib. However, due to the significant number of adverse events, debatable efficiency and resistance, there is a need for novel RET-specific TKIs. Newer RET-specific TKIs are expected to overcome previous limitations and improve patient outcomes. Herein, we aim to review MTC signaling pathways, the most recent options for treatment and the applications for personalized medicine.

Genomic profiling of lymph node and distant metastases from papillary and poorly differentiated thyroid carcinomas

“…Of note, and akin to what was previously observed in the DMs from PDTCs [2], BRAF hotspot mutations do not seem to be a driver of the bone metastasis from either PTC or PDTC patients. In addition, and considering the presence of RET rearrangements already identi ed in 1-3% of non-small cell lung cancers [12], and the poor overall survival already demonstrated in advanced PTC patients harboring such translocations [2], we re-highlight the need of using highly speci c small-molecule RET inhibitors [13] in patients with RET-rearranged advanced TCs.…”