Molecular diagnosis and therapy of kidney cancer.
Molecular diagnosis and therapy of kidney cancer.
复制标题
DOI：
10.1146/annurev.med.042808.171650
复制
发表时间：
2010
影响因子：
10.5
通讯作者：
Srinivasan R
中科院分区：
文献类型：
--
作者：
Linehan WM;Bratslavsky G;Pinto PA;Schmidt LS;Neckers L;Bottaro DP;Srinivasan R
肾癌不是一种单一的疾病;它是由许多发生在肾脏中的癌症组成的，每种癌症具有不同的组织学，具有不同的临床过程，对治疗的反应不同，并且由不同的基因引起。了解肾癌的遗传基础对这种疾病的诊断和管理具有重要意义。VHL基因是肾透明细胞癌的基因。VHL蛋白形成靶向缺氧诱导因子的复合物，用于泛素介导的降解。对这一途径的了解为开发许多新的治疗方法提供了基础，这些方法已被FDA批准用于治疗这种疾病。MET基因是1型乳头状肾癌的遗传形式的基因，并且已经发现在散发性1型乳头状肾癌的子集中发生突变。目前正在进行针对散发性和遗传性乳头状肾癌MET酪氨酸激酶结构域的药物的临床试验。BHD基因是遗传性嫌色肾癌的基因。BHD基因被认为通过AMPK和mTOR信号通路参与能量和/或营养感测。遗传性平滑肌瘤病肾细胞癌是2型乳头状肾癌的一种遗传形式，由克雷布斯循环酶延胡索酸水合酶（延胡索酸水合酶，FH）失活引起。FH活性的丧失已被证明以VHL非依赖性方式改变缺氧诱导因子（HIF）的降解。这些肾癌基因通路的知识使这种疾病的管理新的方法，并为这种疾病的靶向治疗的发展提供了基础。
Kidney cancer is not a single disease; it is made up of a number of cancers that occur in the kidney, each with a different histology, having a different clinical course, responding differently to therapy and caused by a different gene. Understanding the genetic basis of cancer of the kidney has significant implications for diagnosis and management of this disease. The VHL gene is the gene for clear cell kidney cancer. The VHL protein forms a complex that targets the hypoxia inducible factors for ubiquitin-mediated degradation. Knowledge of this pathway has provided the foundation for the development of a number of novel therapeutic approaches that have been approved by the FDA for treatment of this disease. The MET gene is the gene for the hereditary form of type 1 papillary renal carcinoma and has been found to be mutated in a subset of sporadic type 1 papillary kidney cancers. Clinical trials are currently ongoing with agents targeting the tyrosine kinase domain of MET in sporadic and hereditary forms of papillary kidney cancer. The BHD gene is the gene for the hereditary type of chromophobe kidney cancer. The BHD gene is thought to be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. Hereditary Leiomyomatosis Renal Cell Carcinoma, a hereditary form of type 2 papillary renal carcinoma, is caused by inactivation of the Krebs cycle enzyme, fumarate hydratase (fumarase, FH). Loss of FH activity has been shown to alter the degradation of hypoxia inducible factor (HIF) in a VHL-independent fashion. Knowledge of these kidney cancer gene pathways has enabled new approaches for the management of this disease and has provided the foundations for the development of targeted therapeutics for this disease.
登录
查看更多内容
影响因子：
6.2
作者：
Crispen, Paul L.;Viterbo, Rosalia;Uzzo, Robert G.
通讯作者：
Uzzo, Robert G.
影响因子：
6.2
作者：
Escudier, Bernard;Goupil, Marine Gross;Fizazi, Karim
通讯作者：
Fizazi, Karim
影响因子：
45.3
作者：
Escudier, Bernard;Eisen, Tim;Bukowski, Ronald M.
通讯作者：
Bukowski, Ronald M.
影响因子：
45.3
作者：
Feldman, Darren R.;Baum, Michael S.;Motzer, Robert J.
通讯作者：
Motzer, Robert J.
影响因子：
56.9
作者：
DUAN, DR;PAUSE, A;KLAUSNER, RD
通讯作者：
KLAUSNER, RD