索拉非尼在碘难治性分化型甲状腺癌中耐药机制现状

Research progress on drug resistance mechanism of sorafenib in radioiodine refractory differentiated thyroid cancer

大多数分化型甲状腺癌症患者在放射性碘-131治疗后预后良好,但仍有少数患者对放射性碘治疗不敏感,甚至依然出现疾病进展。目前,一些可以提高放射性碘难治性分化型甲状腺癌症患者无进展生存率的靶向药物,如索拉非尼和乐伐替尼,已被批准用于治疗放射性碘难治性分化型癌症(RAIR-DTC)。然而,由于原发性和继发性耐药的存在,药物对这些患者的疗效并不理想。本综述就丝裂原活化蛋白激酶(MAPK)和磷脂酰肌醇3-激酶(PI3K)通路介绍索拉非尼继发性耐药机制并提出相关治疗策略,以期为索拉非尼类似药物耐药机制与放射性碘难治性分化型甲状腺癌的有效治疗提供参考依据。

Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.