Graduate School, Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
Ruikang Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
Medicine (Baltimore). 2024 Jul 26;103(30):e38991. doi: 10.1097/MD.0000000000038991.
Immune checkpoint inhibitor (ICI) combinations, as well as ICIs combined with tyrosine kinase inhibitors, have considerable potential for renal cell carcinoma (RCC) treatment. Newer targeted medications, gut microbiome, nanomedicines, and cyclin-dependent kinase (CDK) inhibitors demonstrate significant potential in preventing side effects and resistance associated with RCC treatment. Most patients, including those demonstrating long-term treatment effects, eventually demonstrate cancer progression. Nevertheless, recent studies have further revealed RCC pathogenesis and many acquired drug resistance mechanisms, which together have led to the identification of promising therapeutic targets. In addition to having roles in metabolism, immunogenicity, and the immune response to tumors, CDK4 and CDK6 regulate the cell cycle. Targeting CDK4 and CDK6, either separately or in combination with already approved treatments, may improve therapeutic outcomes in patients with kidney cancer. Other novel drugs, including pegylated interleukin 10, colony-stimulating factor 1 receptor inhibitors, CD40 agonists, and C-X-C receptor 4 inhibitors affect the tumor microenvironment and cancer cell metabolism. Moreover, a triple ICI combination has been noted to be efficacious. In general, compared with sunitinib as a single-drug treatment, newer ICI combinations improve overall survival in patients with RCC. Future research on the prevention of adverse events and medication resistance related to newer therapies may aid in ensuring effective treatment outcomes among patients with RCC. This article aims to summarize innovative immunotherapy drug combinations for RCC treatment and the mechanisms of action, drug resistance, and treatment of adverse events associated with these combinations.
免疫检查点抑制剂 (ICI) 联合治疗，以及 ICI 联合酪氨酸激酶抑制剂治疗，在肾癌 (RCC) 治疗方面具有很大的潜力。新型靶向药物、肠道微生物组、纳米药物和细胞周期蛋白依赖性激酶 (CDK) 抑制剂在预防与 RCC 治疗相关的副作用和耐药性方面显示出很大的潜力。大多数患者，包括那些表现出长期治疗效果的患者，最终都会出现癌症进展。然而，最近的研究进一步揭示了 RCC 的发病机制和许多获得性耐药机制，这些共同导致了有前途的治疗靶点的确定。CDK4 和 CDK6 除了在代谢、免疫原性和对肿瘤的免疫反应中发挥作用外，还调节细胞周期。针对 CDK4 和 CDK6，无论是单独靶向还是与已批准的治疗联合靶向，都可能改善肾癌患者的治疗效果。其他新型药物，包括聚乙二醇化白细胞介素 10、集落刺激因子 1 受体抑制剂、CD40 激动剂和 C-X-C 受体 4 抑制剂，都能影响肿瘤微环境和癌细胞代谢。此外，三重 ICI 联合治疗已被证明是有效的。总的来说，与单药治疗舒尼替尼相比，新型 ICI 联合治疗可提高 RCC 患者的总生存期。未来对与新型疗法相关的不良反应和耐药性预防的研究，可能有助于确保 RCC 患者的治疗效果。本文旨在总结用于 RCC 治疗的创新免疫治疗药物联合治疗以及这些联合治疗相关的作用机制、耐药性和不良反应的处理。
