Hereditary kidney cancer: unique opportunity for disease-based therapy.
Hereditary kidney cancer: unique opportunity for disease-based therapy.
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DOI：
10.1002/cncr.24230
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发表时间：
2009-05-15
期刊：
影响因子：
6.2
通讯作者：
Srinivasan R
中科院分区：
文献类型：
--
作者：
Linehan WM;Pinto PA;Bratslavsky G;Pfaffenroth E;Merino M;Vocke CD;Toro JR;Bottaro D;Neckers L;Schmidt LS;Srinivasan R
肾癌不是一种单一的疾病；它由许多不同类型的癌症组成，每一种都有不同的组织学，不同的临床过程，由不同的基因引起，对治疗的反应也不同。VHL基因是遗传性癌症综合征（von Hippel-Lindau）的基因，也是散发性、非遗传性透明细胞肾癌的常见基因。了解VHL-HIF通路为开发一些靶向该通路的药物提供了基础，如舒尼替尼、索拉非尼和替西莫司。遗传性乳头状肾癌（HPRC）是一种遗传性肾癌综合征，患者有发展为双侧多灶1型乳头状肾细胞癌的风险。HPRC潜在的遗传缺陷是MET，即肝细胞生长因子（HGF）的细胞表面受体。在散发性1型乳头状肾细胞癌患者的肿瘤亚群中也发现了MET突变。针对MET途径的临床试验正在HPRC患者以及散发性（非遗传性）乳头状肾癌患者中进行。BHD（也称为FLCN）基因是birt - hogg - dub<s:1>综合征的基因，这是一种常染色体显性遗传性皮肤病，与遗传性恐色症和嗜癌细胞混合型RCC有关。针对BHD基因通路的临床前研究正在进行中，为birt - hogg - dub<s:1>和散发性憎色性RCC的临床试验做准备。遗传性平滑肌瘤病肾细胞癌（HLRCC）患者有发展为皮肤和子宫平滑肌瘤的风险，这是一种非常侵袭性的RCC类型。HLRCC的特征是克雷布斯循环酶富马酸水合酶（FH）的种系突变。TCA循环和VHL-HIF途径的研究为hlrc相关肾癌以及其他遗传性和散发型RCC患者的治疗方法提供了基础。
Kidney cancer is not a single disease; it is made up of a number of different types of cancer, each with a different histology, a different clinical course, caused by a different gene, and responding differently to therapy. The VHL gene is the gene for the hereditary cancer syndrome, von Hippel-Lindau, as well as for the common form of sporadic, non-inherited, clear cell kidney cancer. Understanding the VHL-HIF pathway has provided the foundation for the development of a number of agents targeting this pathway, such as sunitinib, sorafenib and temsirolimus. Hereditary Papillary Renal Carcinoma (HPRC) is a hereditary renal cancer syndrome in which affected individuals are at risk for the development of bilateral, multifocal, type 1 papillary renal cell carcinoma. The genetic defect underlying HPRC is MET, the cell surface receptor for hepatocyte growth factor (HGF). Mutations of MET have also been found in a subset of tumors from patients with sporadic type 1 papillary renal cell carcinoma. Clinical trials targeting the MET pathway are underway in patients with HPRC as well as patients with sporadic (non-hereditary) papillary kidney cancer. The BHD (also known as FLCN) gene is the gene for Birt-Hogg-Dubé syndrome, an autosomal dominant genodermatosis associated with a hereditary form of chromophobe, and oncocytic hybrid RCC. Preclinical studies are underway targeting the BHD gene pathway in preparation for clinical trials in Birt-Hogg-Dubé and sporadic chromophobe RCC. Hereditary Leiomyomatosis Renal Cell Carcinoma (HLRCC) patients are at risk for the development of cutaneous and uterine leiomyomas and a very aggressive type of RCC. HLRCC is characterized by germline mutation of the Krebs cycle enzyme, fumarate hydratase (FH). Studies of the TCA cycle and VHL-HIF pathways have provided the foundation for therapeutic approaches in patients with HLRCC-associated kidney cancer, as well as other hereditary and sporadic forms of RCC.
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影响因子：
158.5
作者：
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