Jikuya Ryosuke, Fukagawa Akihiko, Ito Daisuke, Ishihara Hiroki, Takemura Kosuke, Kashima Soki, Kato Taigo, Urabe Fumihiko
Department of Urology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Int J Urol. 2025 Aug;32(8):932-943. doi: 10.1111/iju.70091. Epub 2025 May 7.
Despite significant progress in the diagnosis and treatment of renal cell carcinoma (RCC), approximately 20% of patients present with metastatic disease, and up to 30% of patients with localized tumors experience recurrence following nephrectomy. Although immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) have improved clinical outcomes, treatment resistance and refractoriness remain critical challenges. Genomic profiling has identified alterations in several kidney cancer-associated genes, including VHL and chromatin remodeling genes, refining the classification of RCCs and revealing novel therapeutic targets such as hypoxia-inducible factor (HIF)-2α and metabolic pathways. Immunologically, RCCs exhibit trends opposite to those observed in other types of cancer, such as melanoma and lung cancer, in that high tumor mutation burden and high CD8+ T cell infiltration in RCCs do not predict better responses to ICIs. Combination therapies integrating ICIs and VEGFR-TKIs have shown greater treatment efficacy, but overcoming immune resistance remains an urgent priority. Liquid biopsy technologies, including assays of circulating tumor DNA and extracellular vesicles, are emerging as minimally invasive tools for early detection, treatment monitoring, and recurrence prediction. Liquid biopsy approaches that Integrate genomic and transcriptomic profiling may provide comprehensive tumor characterization and suggest personalized treatment strategies. This review explores recent advances in basic and translational research, emphasizing genomic analyses, dissection of tumor-immune microenvironments, and liquid biopsy techniques that can reshape RCC diagnostics and therapeutics. Multidisciplinary collaboration supported by high-quality biospecimens and robust clinical datasets is essential to advance translational research and improve patient outcomes.
尽管肾细胞癌（RCC）的诊断和治疗取得了显著进展，但仍有大约20%的患者出现转移性疾病，高达30%的局限性肿瘤患者在肾切除术后会复发。虽然免疫检查点抑制剂（ICIs）和血管内皮生长因子受体酪氨酸激酶抑制剂（VEGFR-TKIs）改善了临床结局，但治疗耐药性和难治性仍然是关键挑战。基因组分析已确定了几种肾癌相关基因的改变，包括VHL和染色质重塑基因，完善了RCC的分类并揭示了新的治疗靶点，如缺氧诱导因子（HIF）-2α和代谢途径。在免疫方面，RCC表现出与其他类型癌症（如黑色素瘤和肺癌）相反的趋势，即RCC中的高肿瘤突变负担和高CD8 + T细胞浸润并不能预测对ICIs有更好的反应。整合ICIs和VEGFR-TKIs的联合疗法已显示出更大的治疗效果，但克服免疫抵抗仍然是当务之急。液体活检技术，包括循环肿瘤DNA和细胞外囊泡检测，正在成为用于早期检测、治疗监测和复发预测的微创工具。整合基因组和转录组分析的液体活检方法可能提供全面的肿瘤特征描述并提出个性化治疗策略。本综述探讨了基础和转化研究的最新进展，重点强调基因组分析、肿瘤免疫微环境剖析以及可重塑RCC诊断和治疗的液体活检技术。由高质量生物标本和强大临床数据集支持的多学科合作对于推进转化研究和改善患者结局至关重要。
