摘要
肾细胞癌是癌症中有不同组织学亚型的异质群体。大多数成人肾肿瘤是透明细胞肾细胞癌,其特点是VHL基因的改变。最新肾癌基因特征的研究进展表明了透明细胞肾细胞癌(ccRCC) 遗传异质性和在染色体3 p上它至少存在3个额外ccRCC肿瘤抑制基因。因失活VHL肾癌细胞产生HIF-responsive VEGF生长因子。PI3K--mTORC1信号轴也代表着一个治疗靶点。新的系统性疗法,包括单克隆抗体、酪氨酸激酶抑制剂、mTOR旨在将抑制血管生成和血管内皮的生长因子作为靶点[1]。VEGF抑制剂被批准用于治疗各种ccRCC和我们将讨论在治疗转移性ccRCC最新展。其他基因改变在遗传性癌症综合征已确定,例如FLCN、TSC1、TSC2、TFE3、TFEB、MITF、FH、SDHB、SDHD、MET和PTEN。我们综述了他们在肾肿瘤的癌变、预后、个体化治疗中起到的作用。通过综述形态学和肾癌分子遗传学之间的关联特性,为肾癌靶点治疗提供基础。
关键词: 肾癌靶向治疗,个体化医学
Current Drug Targets
Title:Oncotargets in Different Renal Cancer Subtypes
Volume: 16 Issue: 2
Author(s): Holger Moch, Rodolfo Montironi, Antonio Lopez-Beltran, Liang Cheng and Axel Mischo
Affiliation:
关键词: 肾癌靶向治疗,个体化医学
摘要: Renal cell cancer is a heterogeneous group of cancers with different histologic subtypes. The majority of renal tumors in adults are clear cell renal cell carcinomas, which are characterized by von Hippel- Lindau (VHL) gene alterations. Recent advances in defining the genetic landscape of renal cancer has shown the genetic heterogeneity of clear cell renal cell carcinomas (ccRCC) and the presence of at least 3 additional ccRCC tumor suppressor genes on chromosome 3p. Due to inactivation of VHL, renal cancer cells produce the HIF-responsive growth factor VEGF. The PI3K--mTORC1 signaling axis also represents a target for therapy. The new systemic therapies, including tyrosine kinase inhibitors, monoclonal antibodies, and mTOR inhibitors, aim to suppress angiogenesis with vascular endothelial growth factor as a target [1]. Various VEGF-inhibitors are approved for the treatment of ccRCC and we discuss recent advancements in the treatment of metastatic ccRCC. Other gene alterations have been identified in hereditary cancer syndromes, e.g. FLCN, TSC1, TSC2, TFE3, TFEB, MITF, FH, SDHB, SDHD, MET, and PTEN and we review their role in renal tumor carcinogenesis, prognosis, and targeted therapy. By reviewing the associations between morphologic features and molecular genetics of renal cancer we provide insight into the basis for targeted renal cancer therapy.
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Holger Moch, Rodolfo Montironi, Antonio Lopez-Beltran, Liang Cheng and Axel Mischo , Oncotargets in Different Renal Cancer Subtypes, Current Drug Targets 2015; 16 (2) . https://dx.doi.org/10.2174/1389450116666150126110632
DOI https://dx.doi.org/10.2174/1389450116666150126110632 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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