Division of Medical Oncology, Department of Oncology, and Endocrine Malignancies Disease Oriented Group, Mayo Clinic Cancer Center, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Division of Endocrinology, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Nat Rev Clin Oncol. 2016 Jul;13(7):403-16. doi: 10.1038/nrclinonc.2016.19. Epub 2016 Mar 1.
Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research.
对治疗特定疾病分子靶点的深入了解，已促使两种药物（凡德他尼和卡博替尼）获得监管部门批准，用于治疗甲状腺髓样癌（MTC），以及两种药物（索拉非尼和仑伐替尼）获得监管部门批准，用于治疗美国和欧盟的放射性碘难治性分化型甲状腺癌（DTC）。然而，这些药物和其他疗法对甲状腺癌患者的总生存和生活质量的影响，仍需要更明确地定义。当早期应用于疾病过程中时，强化多模式治疗似乎可以改善间变性甲状腺癌（ATC）患者的生存结局，但 ATC 的挽救治疗的获益尚不确定。针对 DTC 和 ATC 患者，目前正在积极开发更多创新性、合理设计的治疗策略，有多项 II 期和 III 期随机临床试验正在进行中。人们正在继续努力，以确定在甲状腺癌中具有潜在治疗相关性的进一步信号通路，并详细阐述信号通路之间的复杂相互作用，以期将这些发现转化为有效和个性化的治疗方法。在此，我们总结了不同组织学类型晚期甲状腺癌的分子医学进展，分析了这些进展如何改变（并可能进一步完善）患者的治疗方法，并确定了未来研究的开放性问题。
