Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263-0001, USA.
Expert Rev Anticancer Ther. 2009 Dec;9(12):1817-27. doi: 10.1586/era.09.157.
Renal cell carcinoma (RCC) is a disease with a variable natural history, sometimes presenting with a very indolent course and other times with an aggressive clinical course and unusual sites of metastasis. Surgical resection for stage I-III tumors represents the standard of care and is the only curative option available to patients. However, 40-50% of patients develop metastatic disease. Prior to the advent of targeted therapy, cytokine therapy was the only treatment for RCC. The administration of high-dose, bolus IL-2 has historically produced consistent, durable responses in a small percentage of patients with advanced RCC. The use of IFN-alpha is currently limited to combination therapies. Multiple new agents targeting the VEGF pathway have been tested and approved, including sunitinib, sorafenib and bevacizumab, with others waiting in the wings. In the majority of cases these drugs induce disease stabilization with eventual disease progression. Hence additional new pathways are being targeted and studied. Mechanisms of drug resistance, novel combinations, sequences and schedules are the focus of current clinical investigations. This review provides an updated list of the novel targeted agents in advanced clinical development for metastatic RCC.
肾细胞癌（RCC）是一种具有多变自然史的疾病，有时表现为非常惰性的病程，而有时则表现为侵袭性的临床病程和不常见的转移部位。对于 I-III 期肿瘤，手术切除是标准的治疗方法，也是患者唯一可获得的治愈方法。然而，40-50%的患者会发生转移疾病。在靶向治疗出现之前，细胞因子治疗是 RCC 的唯一治疗方法。高剂量、冲击 IL-2 的给药在一小部分晚期 RCC 患者中产生了一致的、持久的反应。IFN-α的应用目前仅限于联合治疗。已经测试和批准了多种针对 VEGF 途径的新型药物，包括舒尼替尼、索拉非尼和贝伐珠单抗，还有其他药物在等待批准。在大多数情况下，这些药物会诱导疾病稳定，最终导致疾病进展。因此，正在针对其他新途径进行研究。药物耐药机制、新的联合用药、顺序和方案是当前临床研究的重点。本文提供了一份最新的、处于晚期临床开发阶段的新型靶向药物的列表，用于治疗转移性肾细胞癌。
