肿瘤细胞治疗研究
英文原题：Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every Decade.
透明细胞肾细胞癌（RCC）的发生主要由 VHL 基因失活驱动，进而导致血管内皮生长因子（VEGF）过表达。
透明细胞肾细胞癌（RCC）的发生主要由VHL基因失活驱动，导致血管内皮生长因子（VEGF）过表达。2000年代，靶向VEGF及其受体（VEGFR）的酪氨酸激酶抑制剂（TKI）改变了转移性肾癌的治疗格局。卡博替尼或仑伐替尼等新一代TKI的出现，使部分患者能够克服对第一代抗VEGFR TKI的耐药机制。2010至2020年间，免疫检查点阻断（ICB）疗法的开发改变了多种实体瘤（包括RCC）的一线及后续治疗。双重ICB或ICB联合抗VEGFR TKI目前已成为晚期透明细胞RCC患者的标准治疗。为优化联合疗法并维持患者生活质量，研究者正在开展前瞻性随机试验，根据患者预后风险评估治疗升级或降阶策略。最后，靶向缺氧诱导因子（HIF），以及开发抗体药物偶联物（ADC）、CAR-T细胞或放射性药物等创新疗法，均有望进一步改善患者生存。
Clear cell renal cell carcinoma (RCC) oncogenesis is mainly driven by VHL gene inactivation, leading to overexpression of vascular endothelial growth factor (VEGF). The use of tyrosine-kinase inhibitors (TKIs) directed against VEGF and its receptor (VEGFR) revolutionised the management of metastatic renal cancer in the 2000s. The more recent development of next-generation TKIs such as cabozantinib or lenvatinib has made it possible to bypass some of the mechanisms of resistance to first-generation anti-VEGFR TKIs. During the decade 2010-2020, the development of immune checkpoint blockade (ICB) therapies revolutionised the management of many solid cancers, including RCC, in first- and subsequent-line settings. Dual ICB or ICB plus anti-VEGFR TKI combinations are now the standard of care for patients with advanced clear cell RCC. To optimise these combination therapies while preserving patient quality of life, escalation and de-escalation strategies are being evaluated in prospective randomised trials, based on patient selection according to their prognosis risk. Finally, new therapeutic approaches, such as targeting hypoxia-inducible factor (HIF) and the development of innovative treatments using antibody-drug conjugates (ADCs), CAR-T cells, or radiopharmaceuticals, are all potential candidates to improve further patient survival.
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