靶向药物在晚期肾癌的个体化应用-外科学(泌尿外科)专业论文.docxVIP

重庆医 重庆医科大学硕士研究生学位论文 万方数据 万方数据 英汉缩略语名词对照 英文缩写 英文全称 中文全称 RCC Renal Cell Carcinoma 肾细胞癌 mRCC Metastatic Renal Cel lCarcinoma 转移性肾癌 FDA Food and Drug Administration 食品与药物管理局 OS Overall Survival 总生存期 PFS Progress Free Survival 无进展生存期 ORR Objective Response Rate 客观缓解率 mTOR mammalian Target Of Rapamycin 哺乳动物雷帕霉素 蛋白 IFN-α Interferon-alpha 干扰素-α TTP Time To Progress 疾病进展时间 VHL Von Hippel-Lindau 希佩尔-林道 DCR Disease Control Rrate 疾病控制率 1 靶向药物在晚期肾癌的个体化应用 摘 要 肾细胞癌是泌尿生殖系统恶性程度最高的肿瘤之一，具有进展快、 病死率高的特点。由于肾癌对放、化疗均不敏感，近 20 年来以白细胞 介素-2 和干扰素-α为主的非特异性免疫治疗成为晚期肾癌的主要治 疗手段，但仅能使约 10%的晚期肾癌病情缓解。近年来，随着对肾癌的 生物学和分子机制的深入研究发现 VHL、Ras 等基因的突变、超甲基化 与肾癌的发生、发展有关，因此将这些与肾癌有关的突变基因及其信 号传导通路作为靶点，针对这些特异性靶点进行封闭或阻断以达到抗 肿瘤作用的多种靶向药物陆续问世，改善了晚期肾癌的预后，为我们 治疗晚期肾癌提供了更多的选择方案。本文将综述晚期肾癌的各类靶 向药物，并从组织学类型、临床特征、生物标记物、药物的毒副反应 等方面分析靶向药物的个体化治疗。 关键词：晚期肾癌，靶向药物，靶向治疗，个体化治疗 2 INDIVIDUALIZED APPLICATION OF TARGETED DRUGS IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA ABSTRACT Renal cell carcinoma(RCC) is one of the highest degree of malignant tumor among the urogenital system, which has characteristics of rapid progression and highly mortality. Due to RCC is not sensitive to radiotherapy and chemotherapy,nonspecific immune therapy, including interleukin - 2 and interferon -α has become the main treatment of advanced RCC in recent 20 years. However, only about 10% of advanced RCC are in remission. Extensive researches about biology and molecular mechanism have found that VHL, Ras gene mutation and hypermethylation are associated with the occurrence and development of RCC. Therefore, these mutant genes and signaling pathways as targets were closed and blocked which acting as targeted drugs have been developed to improve the prognosis of advanced RCC and offer more options for the treatment of advanced RCC. This article reviewed the various of targeted drugs for treatment advanced RCC, and analyzed individual therapy of targeting 3 drugs in terms of histological type, clinical characteristics, biomarkers, drug toxicity, etc. Key words: Adv