Clinical and Translational Challenges in Thyroid Cancer.

Thyroid cancer is the most common endocrine malignancy and it accounts for 1% of all newly diagnosed tumors. Approximately 10% of patients with differentiated thyroid carcinomas (DTC) and 30% with medullary thyroid carcinoma (MTC) could not be cured with locoregional treatment and could develop metastatic disease. In addition, one of the most aggressive solid tumors can arise from the thyroid gland, the anaplastic thyroid carcinoma, with a median overall survival of less than 6 months. Currently, only four drugs are approved for the treatment of DTC and MTC and several unmet needs are focusing the scientific discussions, including the resistant setting, the off-target side effects that may reduce the efficacy and the molecular knowledge-based combinations. In this review, we aimed to discuss the current molecular landscape and treatment of thyroid cancers, and the ongoing clinical and translational research lines focusing on new drugs and drug combinations to improve the inhibition of driver mutations, such as BRAF and RET, and how systemic therapies that improved outcomes of other cancer types, like immunotherapy and peptide receptor radionuclide therapy, may play a role in the future management of advanced thyroid cancers.