Siska Peter J, Beckermann Kathryn E, Rathmell W Kimryn, Haake Scott M
Departments of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, 2220 Pierce Ave, PRB 646, Nashville, TN 37232. TEL: (615) 936-2003; FAX: (615) 343-7602.
Division of Hematology and Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2220 Pierce Ave, PRB 646, Nashville, TN 37232. TEL: (615) 936-2003; FAX: (615) 343-7602.
Urol Oncol. 2017 Mar;35(3):102-110. doi: 10.1016/j.urolonc.2016.12.002. Epub 2017 Jan 11.
Renal cell cancer (RCC) is a prevalent and lethal disease. At time of diagnosis, most patients present with localized disease. For these patients, the standard of care includes nephrectomy with close monitoring thereafter. While many patients will be cured, 5-year recurrence rates range from 30% to 60%. Furthermore, nearly one-third of patients present with metastatic disease at time of diagnosis. Metastatic disease is rarely curable and typically lethal. Cytotoxic chemotherapy and radiation alone are incapable of controlling the disease. Extensive effort was expended in the development of cytokine therapies but response rates remain low. Newer agents targeting angiogenesis and mTOR signaling emerged in the 2000s and revolutionized patient care. While these agents improve progression free survival, the development of resistance is nearly universal. A new era of immunotherapy is now emerging, led by the checkpoint inhibitors. However, therapeutic resistance remains a complex issue that is likely to persist.
In this review, we systematically evaluate preclinical research and clinical trials that address resistance to the primary RCC therapies, including anti-angiogenesis agents, mTOR inhibitors, and immunotherapies. As clear cell RCC is the most common adult kidney cancer and has been the focus of most studies, it will be the focus of this review.
肾细胞癌（RCC）是一种常见的致命疾病。在诊断时，大多数患者表现为局限性疾病。对于这些患者，标准治疗包括肾切除术，术后密切监测。虽然许多患者可以治愈，但5年复发率在30%至60%之间。此外，近三分之一的患者在诊断时已出现转移性疾病。转移性疾病很少能治愈，通常是致命的。单纯的细胞毒性化疗和放疗无法控制疾病。在细胞因子疗法的研发上投入了大量精力，但有效率仍然很低。21世纪出现了针对血管生成和mTOR信号传导的新型药物，彻底改变了患者的治疗方式。虽然这些药物可改善无进展生存期，但耐药性的产生几乎是普遍现象。现在，以检查点抑制剂为首的免疫疗法新时代正在兴起。然而，治疗耐药性仍然是一个复杂的问题，很可能会持续存在。
在本综述中，我们系统地评估了针对原发性RCC治疗耐药性的临床前研究和临床试验，包括抗血管生成药物、mTOR抑制剂和免疫疗法。由于透明细胞RCC是最常见的成人肾癌，且一直是大多数研究的重点，因此它将是本综述的重点。
