Molecular targets of tyrosine kinase inhibitors in thyroid cancer
Molecular targets of tyrosine kinase inhibitors in thyroid cancer
复制标题
DOI：
10.1016/j.semcancer.2020.11.013
复制
发表时间：
2022-02-12
影响因子：
14.5
通讯作者：
Antonelli, Alessandro
中科院分区：
文献类型：
--
作者：
Fallahi, Poupak;Ferrari, Silvia Martina;Antonelli, Alessandro
甲状腺癌（TC）是全球第八大最常见的癌症，在过去20年中发病率不断上升。手术是髓样TC（MTC）和分化型TC（DTC）的主要治疗策略。在DTC患者中，甲状腺切除术后给予放射性碘（RAI）。颈部超声、基础和促甲状腺激素刺激的甲状腺球蛋白通常在第一年每3至6个月进行一次，随后的间隔取决于初始风险评估，以检测随访期间可能的持续/复发疾病。在诊断时，与5%的DTC患者相似，存在远处转移;高达15%的患者在随访期间复发，10年生存率降低（70%-50%）。在肿瘤进展过程中，DTC癌细胞的碘摄取能力会丧失，使其对RAI不敏感，对预后有负面影响。已经开发了几种抑制信号激酶或致癌激酶（BRAF（V600 E）、RET/PTC）的药物，例如与血小板衍生生长因子受体和血管内皮生长因子受体相关的那些。酪氨酸激酶受体参与癌细胞增殖、血管生成和淋巴管生成。几种酪氨酸激酶抑制剂（TKI）正在成为DTC、MTC和间变性TC（ATC）的新治疗方法，并可诱导临床反应并稳定疾病。乐伐替尼和索拉非尼获得批准用于RAI难治性DTC，而卡博替尼和凡德他尼用于MTC。这些TKI延长了中位无进展生存期，但不会增加总生存期。接受TKI治疗的TC患者可能会出现严重的副作用和耐药性。需要进一步的研究，以确定一个潜在的有效的靶向治疗侵袭性TC，根据其分子特征。
Thyroid cancer (TC) is the eighth most frequently diagnosed cancer worldwide with a rising incidence in the past 20 years. Surgery is the primary strategy of therapy for patients with medullary TC (MTC) and differentiated TC (DTC). In DTC patients, radioactive iodine (RAI) is administered after thyroidectomy. Neck ultrasound, basal and thyroid-stimulating hormone-stimulated thyroglobulin are generally performed every three to six months for the first year, with subsequent intervals depending on initial risk assessment, for the detection of possible persistent/recurrent disease during the follow up. Distant metastases are present at the diagnosis in similar to 5 % of DTC patients; up to 15 % of patients have recurrences during the follow up, with a survival reduction (70 %-50 %) at 10-year. During tumor progression, the iodide uptake capability of DTC cancer cells can be lost, making them refractory to RAI, with a negative impact on the prognosis.Significant advances have been done recently in our understanding of the molecular pathways implicated in the progression of TCs. Several drugs have been developed, which inhibit signaling kinases or oncogenic kinases (BRAF(V600E), RET/PTC), such as those associated with Platelet-Derived Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor.Tyrosine kinase receptors are involved in cancer cell proliferation, angiogenesis, and lymphangiogenesis. Several tyrosine kinase inhibitors (TKIs) are emerging as new treatments for DTC, MTC and anaplastic TC (ATC), and can induce a clinical response and stabilize the disease. Lenvatinib and sorafenib reached the approval for RAI-refractory DTC, whereas cabozantinib and vandetanib for MTC. These TKIs extend median progression-free survival, but do not increase the overall survival. Severe side effects and drug resistance can develop in TC patients treated with TKIs. Additional studies are needed to identify a potential effective targeted therapy for aggressive TCs, according to their molecular characterization.