Department of Health Sciences, University 'Magna Graecia' of Catanzaro, Campus 'S. Venuta', Catanzaro, Italy.
Endocrinology Clinic, Internal Medicine Department, Institut Jules Bordet Comprehensive Cancer Center, Université Libre de Bruxelles, Bruxelles, Belgium.
Curr Opin Oncol. 2020 Jan;32(1):13-19. doi: 10.1097/CCO.0000000000000593.
Radioiodine-refractory thyroid cancers represent the main cause of thyroid cancer-related death. At present, targeted therapies with multikinase inhibitors represent a unique therapeutic tool, though they have limited benefit on patient survival and severe drug-associated adverse events. This review summarizes current treatment strategies for radioiodine-refractory thyroid cancer and focuses on novel approaches to redifferentiate thyroid cancer cells to restore responsiveness to radioiodine administration.
We summarize and discuss recent clinical trial findings and early data from real-life experiences with multikinase-inhibiting drugs. Possible alternative strategies to traditional redifferentiation are also discussed.
The current review focuses primarily on the major advancements in the knowledge of the pathophysiology of iodine transport and metabolism and the genetic and epigenetic alterations occurring in thyroid neoplasia as described using preclinical models. Results of clinical studies employing new compounds to induce thyroid cancer cell redifferentiation by acting against specific molecular targets are also discussed. Finally, we describe the current scenario emerging from such findings as well as future perspectives.
放射性碘难治性甲状腺癌是导致甲状腺癌相关死亡的主要原因。目前，多激酶抑制剂的靶向治疗是一种独特的治疗手段，尽管它们对患者的生存和严重的药物相关不良反应仅有有限的益处。本文总结了放射性碘难治性甲状腺癌的当前治疗策略，并重点介绍了使甲状腺癌细胞重新分化以恢复对放射性碘治疗的反应的新方法。
我们总结和讨论了多激酶抑制药物的最新临床试验结果和真实世界经验的早期数据。还讨论了可能替代传统分化的替代策略。
本综述主要集中于对碘转运和代谢的病理生理学以及甲状腺肿瘤中发生的遗传和表观遗传改变的认识的主要进展，这些内容是使用临床前模型描述的。还讨论了使用新化合物通过针对特定分子靶点来诱导甲状腺癌细胞重新分化的临床研究结果。最后，我们描述了这些发现所带来的当前情况和未来展望。
