Department of Medical Oncology, Medway NHS Foundation Trust, Kent, U.K.
Department of Urology, Medway NHS Foundation Trust, Kent, U.K.
Anticancer Res. 2023 Nov;43(11):4781-4792. doi: 10.21873/anticanres.16675.
Renal cell carcinoma (RCC) is the prevalent form of kidney cancer in adults, with clear cell renal carcinoma (ccRCC) being the predominant subtype. While surgical resection remains the primary curative approach for localized RCC, a significant number of patients encounter disease relapse. The advent of targeted therapies, including tyrosine kinase inhibitors (TKI), mammalian target of rapamycin (mTOR) inhibitors, and immune checkpoint inhibitors, has revolutionized the treatment of metastatic RCC. However, despite therapeutic advancements, the emergence of resistance poses a significant challenge. Resistance mechanisms in RCC involve the disruption of hypoxia pathways, activation of the PI3K/AKT/mTOR pathway, and increased expression of alternate proangiogenic factors. Furthermore, the sequestration of TKI within lysosomes contributes to reduced drug effectiveness and development of resistance. Current research is focused on overcoming resistance by identifying predictive biomarkers for treatment efficacy, developing novel variations of existing therapies that target alternative signalling pathways, and exploring combination therapy approaches. The objective of this review article was to provide a comprehensive assessment of resistance mechanisms to systemic therapies and explore emerging treatment strategies for RCC.
肾细胞癌（RCC）是成人中常见的肾癌形式，其中透明细胞肾细胞癌（ccRCC）是主要亚型。虽然手术切除仍然是局部 RCC 的主要治疗方法，但仍有相当数量的患者出现疾病复发。靶向治疗的出现，包括酪氨酸激酶抑制剂（TKI）、哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂和免疫检查点抑制剂，彻底改变了转移性 RCC 的治疗方法。然而，尽管有了治疗进展，但耐药性的出现仍然是一个重大挑战。RCC 中的耐药机制涉及缺氧途径的破坏、PI3K/AKT/mTOR 途径的激活以及替代促血管生成因子的表达增加。此外，TKI 在溶酶体中的隔离导致药物有效性降低和耐药性的发展。目前的研究重点是通过确定治疗效果的预测生物标志物、开发针对替代信号通路的现有治疗方法的新变体以及探索联合治疗方法来克服耐药性。本文的目的是全面评估系统治疗的耐药机制，并探讨 RCC 的新兴治疗策略。
