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 (TKI) 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. Mol Cancer Ther; 17(7); 1355–64. ©2018 AACR.

中文翻译：

---

透明细胞肾细胞癌对全身治疗的抵抗：机制和管理策略

肾细胞癌 (RCC) 是最常见的肾癌形式。它分为各种亚型，透明细胞 RCC (ccRCC) 约占所有 RCC 肿瘤的 85%。对化学疗法和放射疗法缺乏敏感性促使人们研究新的治疗方案。靶向治疗的发展，包括多靶向酪氨酸激酶抑制剂（TKI）和 mTOR 抑制剂，一直是 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、肿瘤微环境和耐药机制的最新进展为尝试将靶向疗法与新一代免疫疗法相结合以利用可能的协同作用奠定了基础。本综述重点关注 ccRCC 全身治疗耐药机制的基础、转化和临床研究的现状。摩尔癌症治疗; 17(7); 1355-64。©2018 AACR。