Resistance to Systemic Therapies in Clear Cell Renal Cell Carcinoma: Mechanisms and Management Strategies.
Resistance to Systemic Therapies in Clear Cell Renal Cell Carcinoma: Mechanisms and Management Strategies.
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DOI：
10.1158/1535-7163.mct-17-1299
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发表时间：
2018-07
影响因子：
5.7
通讯作者：
Kolenko VM
中科院分区：
文献类型：
--
作者：
Makhov P;Joshi S;Ghatalia P;Kutikov A;Uzzo RG;Kolenko VM
肾细胞癌（RCC）是肾癌最常见的形式。它被分类为各种亚型，透明细胞RCC（ccRCC）占所有RCC肿瘤的约85%。对化疗和放疗缺乏敏感性促使人们努力研究新的治疗方案。靶向治疗剂的开发，包括多靶向酪氨酸激酶抑制剂（TKI）和mTOR抑制剂，是ccRCC治疗的重大突破。最近，包括免疫检查点抑制剂在内的其他治疗策略已成为针对晚期ccRCC的有效治疗选择。此外，疾病生物学、肿瘤微环境和抗性机制的最新进展形成了尝试将联合收割机靶向治疗与新一代免疫治疗结合以利用可能的协同作用的基础。本文综述了ccRCC系统治疗耐药机制的基础、转化和临床研究现状。
Renal cell carcinoma (RCC) is the most common form of kidney cancer. It is categorized into various subtypes, with clear cell RCC (ccRCC) representing about 85% of all RCC tumors. The lack of sensitivity to chemotherapy and radiation therapy prompted research efforts into novel treatment options. The development of targeted therapeutics, including multi-targeted tyrosine kinase inhibitors (TKIs) and mTOR inhibitors, has been a major breakthrough in ccRCC therapy. More recently, other therapeutic strategies, including immune checkpoint inhibitors, have emerged as effective treatment options against advanced ccRCC. Furthermore, recent advances in disease biology, tumor microenvironment, and mechanisms of resistance formed the basis for attempts to combine targeted therapies with newer generation immunotherapies to take advantage of possible synergy. This review focuses on the current status of basic, translational, and clinical studies on mechanisms of resistance to systemic therapies in ccRCC.