Abstract
The knowledge on thyroid cancer biology has grown over the past decade. Thus, diagnostic and therapeutic strategies to manage thyroid cancer are rapidly evolving. With new insights into tumor biology and cancer genetics, several novel therapies have been approved for the treatment of thyroid cancer. Tyrosine kinase inhibitors (TKIs), such as lenvatinib and sorafenib, have been successfully utilized for the treatment of radioactive iodine (RAI)-refractory metastatic differentiated thyroid cancer (DTC). In addition, pretreatment with mitogen-activated protein kinase (MAPK) inhibitors (trametinib and selumetinib) has been shown to restore RAI avidity in previously RAI-refractory DTCs. Local therapies, such as external beam radiation and radiofrequency/ethanol ablation, have also been employed for treatment of DTC. Vandetanib and cabozantinib are the two TKIs currently approved by the Food and Drug Administration (FDA) for the treatment of medullary thyroid cancer (MTC). Other novel therapies, such as peptide receptor radionuclide therapy and carcinoembryonic antigen (CEA) vaccine, have also been utilized in treating MTC. Ongoing trials on selective rearranged-during-transfection (RET) protooncogene inhibitors, such as LOXO-292 and BLU-667, have demonstrated promising results in the treatment of metastatic MTC resistant to non-selective TKIs. The FDA-approved BRAF/MEK inhibitor combination of dabrafenib and trametinib has revolutionized treatment of BRAFV600E mutation positive anaplastic thyroid cancer. Several other emerging classes of medications, such as gene fusion inhibitors and immune checkpoint inhibitors, are being actively investigated in several clinical trials. In this review, we describe the molecular landscape of thyroid cancer and novel targeted therapies and treatment combinations available for the treatment of metastatic thyroid cancer.
Highlights
Thyroid cancer is predicted to affect 52,890 new patients in the USA in 2020, with the incidence being three times higher in women as compared with men [1]
A similar concept is being utilized in another ongoing multicentric prospective non-randomized phase II trial with two independent arms studying the use of trametinib for NRAS mutation-harboring tumors and dabrafenib for BRAFV600E -harboring tumors (Table 2)
Peptide Receptor Radionuclide Therapy in Thyroid Cancer. Another therapeutic concept utilizing radiolabeled agents for treatment of metastatic thyroid cancer had been based on a subset of thyroid cancer expresses somatostatin receptors (SSTR) that could be targeted with peptide receptor radionuclide therapy (PRRT) [128,129]
Summary
Thyroid cancer is predicted to affect 52,890 new patients in the USA in 2020, with the incidence being three times higher in women as compared with men [1]. Metastatic RAI-non-avid disease carries a worse prognosis, as the five-year survival is estimated to be as low as 10% [3]. The overall 10-year survival for MTC confined to the thyroid gland is 95.6% but is as low as 40% for patients with distant metastatic disease at the time of diagnosis [6]. Since standard RAI therapy for DTC is not effective in 5–22% of patients, and surgical treatment is not curative in patients with MTC presenting with metastatic disease, small molecules have been developed that target aberrant signaling pathways found in thyroid cancer [3]. Understanding of the molecular landscape of thyroid cancer is crucial to provide individualized targeted therapies
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