Renal cell carcinoma (RCC) is one of the most lethal urologic malignancies. Partial or radical nephrectomy is the major surgical management for localized RCC, however, almost 30% of patients will develop recurrence and metastasis after surgery. Metastatic RCC (mRCC) is a disease with a very poor prognosis, and the 5-year survival of the mRCC is commonly less than 10%. Unfortunately, mRCC is highly resistant to chemo and radiotherapy. Therefore, mRCC treatment has become a big challenge for researchers as well as clinicians. RCC is characterized as clear genetic background, especially with von Hippel-Lindau (VHL) gene loss or mutation in more than 70% of the cases. Several molecular factors and signaling pathways have been discovered to possess impact on the progression of RCC, including VHL-HIF-VEGF angiogenesis signaling, PI3K/AKT/mTOR signaling, epithelial-to-mesenchymal transition-related pathways, and Wnt/β-catenin pathway, which play crucial roles in the growth, invasiveness, metastasis and angiogenesis of RCC. Based on the recent studies of these signaling pathways, some medicines as well as immune check-point inhibitors have been developed, which have shown potential therapeutic effects for mRCC. Therefore, our current review aims to summarize the recent progress of the treatment for mRCC, with a special focus on the strategies to improve the responsiveness of medicines in patients with mRCC.

肾细胞癌 (RCC) 是最致命的泌尿系统恶性肿瘤之一。部分或根治性肾切除术是局限性 RCC 的主要手术治疗方法，然而，近 30% 的患者在手术后会发生复发和转移。转移性 RCC (mRCC) 是一种预后极差的疾病，mRCC 的 5 年生存率通常低于 10%。不幸的是，mRCC 对化疗和放疗具有很强的抵抗力。因此，mRCC 治疗已成为研究人员和临床医生的一大挑战。RCC 的特征是明确的遗传背景，尤其是 von Hippel-Lindau (VHL) 基因丢失或突变的病例超过 70%。已发现几种分子因素和信号通路对 RCC 的进展具有影响，包括 VHL-HIF-VEGF 血管生成信号、PI3K/AKT/mTOR 信号、上皮间质转化相关通路和 Wnt/β-catenin 通路在 RCC 的生长、侵袭、转移和血管生成中起关键作用。基于最近对这些信号通路的研究，已经开发了一些药物以及免疫检查点抑制剂，这些药物已显示出对 mRCC 的潜在治疗效果。因此，我们目前的综述旨在总结 mRCC 治疗的最新进展，特别关注提高 mRCC 患者药物反应的策略。已经开发了一些药物以及免疫检查点抑制剂，已显示出对 mRCC 的潜在治疗效果。因此，我们目前的综述旨在总结 mRCC 治疗的最新进展，特别关注提高 mRCC 患者药物反应的策略。已经开发了一些药物以及免疫检查点抑制剂，已显示出对 mRCC 的潜在治疗效果。因此，我们目前的综述旨在总结 mRCC 治疗的最新进展，特别关注提高 mRCC 患者药物反应的策略。