Gulec Seza A, Benites Cristina, Cabanillas Maria E
Miami Cancer Research Center, Miami, FL 33181, USA.
Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
J Clin Med. 2024 Jun 21;13(13):3645. doi: 10.3390/jcm13133645.
Thyroid cancer molecular oncogenesis involves functional dedifferentiation. The initiating genomic alterations primarily affect the MAPK pathway signal transduction and generate an enhanced ERK output, which in turn results in suppression of the expression of transcription of the molecules of iodine metabolomics. The clinical end result of these molecular alterations is an attenuation in of radioactive iodine (RAI). The utilization of RAI in systemic therapy of metastatic disease requires restoration of the functional differentiation. This concept has been accomplished by modulation of MAPK signaling. Objective responses have been demonstrated in metastatic disease settings. RAI-refractoriness in "differentiated thyroid cancers" remains a clinical problem despite optimized RAI administration protocols. Functional and associated are the underlying primary obstacles. MAPK pathway modulation offers a potential for reversal of RAI-indifference and combat refractoriness. This review presents the latest clinical experience and protocols for the redifferentiation of radioiodine-refractory thyroid cancer, providing a comprehensive overview of the current protocols and intervention strategies used by leading institutions. Timing and techniques of imaging, thyrotropin (TSH) stimulation methods, and redifferentiation agents are presented. The efficacy and limitations of various approaches are discussed, providing an overview of the advantages and disadvantages associated with each of the protocols.
甲状腺癌分子肿瘤发生涉及功能去分化。起始基因组改变主要影响丝裂原活化蛋白激酶（MAPK）信号转导途径并产生增强的细胞外信号调节激酶（ERK）输出，这反过来又导致碘代谢组学分子转录表达的抑制。这些分子改变的临床最终结果是放射性碘（RAI）摄取减少。在转移性疾病的全身治疗中使用RAI需要恢复功能分化。这一概念已通过调节MAPK信号得以实现。在转移性疾病情况下已证实有客观反应。尽管有优化的RAI给药方案，但“分化型甲状腺癌”中的RAI难治性仍然是一个临床问题。功能去分化及相关因素是根本的主要障碍。MAPK途径调节为逆转RAI不敏感性和对抗难治性提供了可能。本综述介绍了放射性碘难治性甲状腺癌再分化的最新临床经验和方案，全面概述了领先机构目前使用的方案和干预策略。介绍了成像的时机和技术、促甲状腺激素（TSH）刺激方法以及再分化药物。讨论了各种方法的疗效和局限性，概述了与每个方案相关的优缺点。
