Gil-Bernabé Sara, García-DeLaFuente Lucía, García-Rostán Ginesa
Pathology Department, Faculty of Medicine, Valladolid University, 47003 Valladolid, Spain.
Group Pathobiology of Cancer: Inter-, Intra-Tumor Heterogeneity and Molecular Targets, Institute of Molecular Genetics and Biomedicine (IBGM), 47003 Valladolid, Spain.
Int J Mol Sci. 2025 Apr 12;26(8):3663. doi: 10.3390/ijms26083663.
Thyroid cancer prevalence has increased in the last few decades. Whereas the majority of well-differentiated histotypes have effective therapeutic options, the most advanced cases lacked successful treatment until recent years. Genomic alterations have emerged as targets for new anti-cancer drugs. This molecular knowledge is gradually being translated into sophisticated approaches for the stratification, management, and therapies of patients with thyroid carcinomas. The genomic characterisation of tumours in clinical assistance serves as a tool for enhancing the prognostic assessment of patients with thyroid cancer and predicting their responses to the agents. The MAPK pathway is the most predominantly activated molecular route in this cancer. Several drugs have been developed to inhibit this pathway at different levels. However, the acquired resistance that emerges is the main problem in their use. Other strategies targeting not only driver mutations but also those that confer aggressive behaviour on tumours can be potential targetable options. Due to the new therapies, patients with the most aggressive histotypes have improved survival rates. Adverse events, although manageable, have a high prevalence among the current therapies. Selective inhibitors, immunotherapies, and the combination of both will play a pivotal role in the treatment and the improvements in overall survival in thyroid cancer patients.
在过去几十年中，甲状腺癌的患病率有所上升。虽然大多数高分化组织学类型有有效的治疗选择，但直到近年来，最晚期的病例仍缺乏成功的治疗方法。基因组改变已成为新型抗癌药物的靶点。这种分子知识正逐渐转化为用于甲状腺癌患者分层、管理和治疗的复杂方法。临床辅助中肿瘤的基因组特征分析是增强甲状腺癌患者预后评估和预测其对药物反应的一种工具。丝裂原活化蛋白激酶（MAPK）通路是这种癌症中最主要被激活的分子途径。已经开发了几种药物在不同水平上抑制该通路。然而，出现的获得性耐药是其使用中的主要问题。其他不仅针对驱动突变而且针对赋予肿瘤侵袭性的突变的策略可能是潜在的可靶向选择。由于新疗法的出现，具有最具侵袭性组织学类型的患者生存率有所提高。不良事件虽然可控，但在当前疗法中发生率很高。选择性抑制剂、免疫疗法以及两者的联合将在甲状腺癌患者的治疗和总体生存率改善中发挥关键作用。
