小分子抑制剂在治疗肾癌中的研究进展  

Drug resistance of tyrosine kinase inhibitors in renal cell carcinoma

作　　者：钱含旭 赵亚烜 杨阳 张寅 QIAN Hanxu;ZHAO Yaxuan;YANG Yang;ZHANG Yin(School of Pharmacy,Binzhou Medical University,Yantai 264003,Shandong,China)

机构地区：[1]滨州医学院药学院,山东烟台264003

出　　处：《中国临床药理学与治疗学》2025年第1期100-109,共10页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金(82103391);山东省自然科学基金(ZR2021MH292,ZR2020QH242)。

摘　　要：酪氨酸激酶抑制剂在转移性肾细胞癌的治疗中发挥着重要的作用。常用的酪氨酸激酶抑制剂,如舒尼替尼、索拉非尼等在治疗肾癌中取得了良好的疗效。然而,部分肾癌病人对这类小分子抑制剂具有天然耐药性,或在治疗过程中产生获得性耐药,导致治疗效果受到限制。小分子抑制剂耐药仍是肾癌治疗中具有挑战性的临床问题。近年来,随着联合免疫检查点抑制剂、其他靶向药物、纳米粒子递送以及化学合成优化等方法的应用,显著改善了患者的预后。这些手段为提高酪氨酸激酶抑制剂在肾癌治疗中的效果提供了新的策略。本文综述了近年来在肾癌研究中常见的酪氨酸激酶抑制剂及其产生耐药的机制与改善耐药性的潜在方式。Tyrosine kinase inhibitors(TKIs)are the key agent in the treatment of renal cell carcinoma(RCC)so far.Drugs such as sunitinib and sorafenib showed significant benefits RCC patients,however,the adverse effect,drug efficacy and drug resistance limited the use of these therapy.Especially the drug resistant issue brings up a big challenge for clinical practice,and the mechanisms underlying are still poorly understood.In recent years,new therapies have been combined with TKIs to improve the treatment outcome.Immunotherapy,combination therapy with other TKIs,targeted nanoparticle delivery,and drug modification are widely studied to improve the efficacies of TKIs and regain the sensitivity.In this review,we summarizes the current understanding of TKI drug resistance and the approaches to regaining drug sensitivity.

关 键 词：肾癌 耐药 酪氨酸激酶抑制剂 肿瘤血管新生 靶向治疗 

分 类 号：R737[医药卫生—肿瘤]