甲状腺癌的分子基础与靶向治疗：进展与机遇。
Molecular basis and targeted therapy in thyroid cancer: Progress and opportunities.
机构信息
Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, Zhejiang 310014, China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
出版信息
Biochim Biophys Acta Rev Cancer. 2023 Jul;1878(4):188928. doi: 10.1016/j.bbcan.2023.188928. Epub 2023 May 29.
Thyroid cancer (TC) is the most prevalent endocrine malignant tumor. Surgery, chemotherapy, radiotherapy, and radioactive iodine (RAI) therapy are the standard TC treatment modalities. However, recurrence or tumor metastasis remains the main challenge in the management of anaplastic thyroid cancer (ATC) and radioiodine (RAI) radioactive iodine-refractory differentiated thyroid cancer (RR-DTC). Several multi-tyrosine kinase inhibitors (MKIs), or immune checkpoint inhibitors in combination with MKIs, have emerged as novel therapies for controlling the progression of DTC, medullary thyroid cancer (MTC), and ATC. Here, we discuss and summarize the molecular basis of TC, review molecularly targeted therapeutic drugs in clinical research, and explore potentially novel molecular therapeutic targets. We focused on the evaluation of current and recently emerging tyrosine kinase inhibitors approved for systemic therapy for TC, including lenvatinib, sorafenib and cabozantinib in DTC, vandetanib, cabozantinib, and RET-specific inhibitor (selpercatinib and pralsetinib) in MTC, combination dabrafenib with trametinib in ATC. In addition, we also discuss promising treatments that are in clinical trials and may be incorporated into clinical practice in the future, briefly describe the resistance mechanisms of targeted therapies, emphasizing that personalized medicine is critical to the design of second-line therapies.
甲状腺癌（TC）是最常见的内分泌恶性肿瘤。手术、化疗、放疗和放射性碘（RAI）治疗是 TC 的标准治疗方法。然而，复发性或肿瘤转移仍然是治疗间变性甲状腺癌（ATC）和放射性碘（RAI）难治性分化型甲状腺癌（RR-DTC）的主要挑战。几种多酪氨酸激酶抑制剂（MKIs）或免疫检查点抑制剂联合 MKIs已成为控制 DTC、甲状腺髓样癌（MTC）和 ATC 进展的新型治疗方法。在这里，我们讨论并总结了 TC 的分子基础，回顾了临床研究中的分子靶向治疗药物，并探讨了潜在的新型分子治疗靶点。我们重点评估了目前和最近批准用于 TC 全身治疗的酪氨酸激酶抑制剂，包括 lenvatinib、sorafenib 和 cabozantinib 在 DTC 中的应用，vandetanib、cabozantinib 和 RET 特异性抑制剂（selpercatinib 和 pralsetinib）在 MTC 中的应用，dabrafenib 联合 trametinib 在 ATC 中的应用。此外，我们还讨论了正在临床试验中的有前途的治疗方法，并简述了靶向治疗的耐药机制，强调个性化医疗对于二线治疗方案的设计至关重要。
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