Strategies to overcome therapeutic resistance in renal cell carcinoma.
Strategies to overcome therapeutic resistance in renal cell carcinoma.
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DOI：
10.1016/j.urolonc.2016.12.002
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Haake SM
中科院分区：
文献类型：
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作者：
Siska PJ;Beckermann KE;Rathmell WK;Haake SM
肾细胞癌（renal cell cancer，RCC）是一种常见的恶性肿瘤.在诊断时，大多数患者表现为局部疾病。对于这些患者，标准治疗包括肾切除术，此后密切监测。虽然许多患者将被治愈，但5年复发率从30%到60%不等。此外，近三分之一的患者在诊断时存在转移性疾病。转移性疾病很少是可治愈的，并且通常是致命的。单靠细胞毒性化疗和放疗是无法控制这种疾病的。在细胞因子疗法的开发方面花费了大量的努力，但反应率仍然很低。靶向血管生成和mTOR信号传导的新药物出现在21世纪，并彻底改变了患者护理。虽然这些药物改善了无进展生存期，但耐药性的发展几乎是普遍的。免疫治疗的新时代正在出现，由检查点抑制剂领导。然而，耐药性仍然是一个复杂的问题，可能会持续存在。在这篇综述中，我们系统地评估了临床前研究和临床试验，这些研究和临床试验解决了对主要RCC疗法的耐药性，包括抗血管生成剂，mTOR抑制剂和免疫疗法。由于透明细胞肾细胞癌是最常见的成人肾癌，并已成为大多数研究的重点，这将是本文的重点。
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.