The oncologist · 2026
Targeted therapies in the management of advanced medullary thyroid cancer.
СтатьяОбзорНазвание и аннотация: Перевод в очереди
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Arain Hameeda Arif, Izhar Azeem, Caretti Rachael, Chen Herbert, Vodopivec Danica M
Аннотация
BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor that contributes disproportionately to thyroid cancer-related mortality. Historically, systemic treatment options for advanced MTC were limited due to poor responsiveness to radioactive iodine and conventional chemotherapy. The development of targeted therapies has significantly transformed disease management.
METHODS: This narrative review summarizes current evidence on targeted therapies for advanced MTC, including multikinase inhibitors (MKIs), selective RET inhibitors, and emerging treatment strategies. Literature on efficacy, safety, resistance mechanisms, and novel therapeutic approaches was evaluated.
RESULTS: First-generation MKIs, including vandetanib and cabozantinib, demonstrated clinical benefit by targeting RET and angiogenic pathways, though off-target toxicities limited tolerability. More recently, selective RET inhibitors, such as selpercatinib and pralsetinib, have shown high response rates and improved safety profiles, establishing them as preferred first-line therapies for RET-mutant MTC. However, pralsetinib's recent market withdrawal due to regulatory challenges highlights the need for additional options. Emerging therapies, including BOS172738, SY-5007, and peptide receptor radionuclide therapy, show promising early results. Resistance mechanisms, including gatekeeper and solvent front mutations, remain a challenge. Advances in clinical biomarkers and novel approaches, such as CAR-T cell therapy, may further support personalized treatment.
CONCLUSION: Targeted therapies have reshaped the management of advanced MTC, with selective RET inhibitors offering improved efficacy and tolerability. Continued research is essential to overcome resistance, expand therapeutic options, and improve patient outcomes.
METHODS: This narrative review summarizes current evidence on targeted therapies for advanced MTC, including multikinase inhibitors (MKIs), selective RET inhibitors, and emerging treatment strategies. Literature on efficacy, safety, resistance mechanisms, and novel therapeutic approaches was evaluated.
RESULTS: First-generation MKIs, including vandetanib and cabozantinib, demonstrated clinical benefit by targeting RET and angiogenic pathways, though off-target toxicities limited tolerability. More recently, selective RET inhibitors, such as selpercatinib and pralsetinib, have shown high response rates and improved safety profiles, establishing them as preferred first-line therapies for RET-mutant MTC. However, pralsetinib's recent market withdrawal due to regulatory challenges highlights the need for additional options. Emerging therapies, including BOS172738, SY-5007, and peptide receptor radionuclide therapy, show promising early results. Resistance mechanisms, including gatekeeper and solvent front mutations, remain a challenge. Advances in clinical biomarkers and novel approaches, such as CAR-T cell therapy, may further support personalized treatment.
CONCLUSION: Targeted therapies have reshaped the management of advanced MTC, with selective RET inhibitors offering improved efficacy and tolerability. Continued research is essential to overcome resistance, expand therapeutic options, and improve patient outcomes.