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肾细胞癌进化发育中的关键分子事件
刘岩1,谭晓洁1*,苏彤1,杜琰1,侯建国2,曹广文1
0
(1. 第二军医大学热带医学与公共卫生学系流行病学教研室, 上海 200433;
2. 第二军医大学长海医院泌尿外科, 上海 200433
*通信作者)
摘要:
癌症的进化发育过程“肿瘤从癌前病变发展到早期原位癌, 再到转移性癌的每一步都伴随着体细胞在承受肿瘤微环境的选择压力下的不断突变、亚克隆的筛选”, 体现了达尔文进化论的基本观点“遗传变异、自然选择、适者生存”。肿瘤异质性是癌症的重要特征, 也是癌症进化发育的具体表现。肾细胞癌(renal cell carcinoma, RCC)是泌尿系统常见肿瘤, 近些年发病率持续增长。由于RCC是少见的对放疗和化疗均不敏感的实体瘤, 实施系统靶向治疗是治疗晚期RCC患者的主要手段。本文主要综述了RCC进化发育过程中的重要分子事件, 从患者间的个体差异以及肿瘤内部两方面体现了RCC的高度异质性特征。阐明由这些重要分子事件组成的RCC进化发育特征, 是挖掘特异性RCC早期诊断标志物以及尽早在人群中开展个体化治疗的必经之路。
关键词:  肾细胞癌  进化  遗传异质性  靶向治疗
DOI:10.3724/SP.J.1008.2014.01315
投稿时间:2014-09-23修订日期:2014-10-25
基金项目:国家自然科学基金(81101928).
Key molecular events in renal carcinogenesis
LIU Yan1,TAN Xiao-jie1*,SU Tong1,DU Yan1,HOU Jian-guo2,CAO Guang-wen1
(1. Department of Epidemiology, Faculty of Tropical Medicine and Public Health, Second Military Medical University, Shanghai 200433, China;
2. Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
*Corresponding author)
Abstract:
Darwin's Theory of Evolution: inherited variation, natural selection and adaption to survive in the environment is vividly manifested by the process of cancer cell evolution. For each step from precancerous lesion to cancer in situ and metastasis, cancer cells continuously mutate and subclones are selected by the pressure from tumor microenvironment. Cancer is characterized by heterogeneity, which is also a reflection of cancer cell evolution. Renal cell carcinoma (RCC) is one of the most common tumors in urinary system and the incidence rate of RCC is rising in recent years. Because RCC is not sensitive to radiotherapy or chemotherapy, systemic targeted therapy is the only option for patients with advanced RCC. This paper reviews the significant molecular events during the evolution of RCC, revealing the high heterogeneity of RCC both in different patients and in the tumor itself. Understanding the characteristics of RCC evolution is a must to search specific molecular markers for early diagnosis and for practice of individualized therapy.
Key words:  renal cell carcinoma  evolution  genetic heterogeneity  targeted therapy