Renal cell carcinoma.

Renal cell carcinoma.
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DOI:
10.1038/nrdp.2017.9
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发表时间:
2017-03-09
期刊:
Nature reviews. Disease primers
影响因子:
--
通讯作者:
Ficarra V
Ficarra V
中科院分区:
其他
文献类型:
--
作者:
Hsieh JJ;Purdue MP;Signoretti S;Swanton C;Albiges L;Schmidinger M;Heng DY;Larkin J;Ficarra V

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肾细胞癌(RCC)是指源自肾上皮的癌症,占肾脏癌症的>90%。该疾病包括>10种组织学和分子学亚型,其中透明细胞RCC(ccRCC)是最常见的,并导致大多数癌症相关死亡。虽然体细胞VHL突变已经描述了一段时间,但最近的癌症基因组研究已经确定了表观遗传学调控基因的突变,并证明了显著的肿瘤内异质性,这可能具有预后,预测和治疗相关性。局部肾细胞癌可以成功地与手术管理,而转移性肾细胞癌是难治性的常规化疗。然而,在过去的十年中,转移性RCC的治疗已经取得了显著的进展,靶向药物包括索拉非尼、舒尼替尼、贝伐单抗、帕唑帕尼和阿昔替尼,其抑制血管内皮生长因子(VEGF)及其受体(VEGFR),以及依维莫司和替西罗莫司,其抑制mTOR复合物1,被批准。自2015年以来,除了VEGFR之外,还批准了其他靶点的药物,如卡博替尼和乐伐替尼;免疫疗法如纳武单抗也被添加到转移性RCC的治疗中。在这里,我们提供了RCC的分子生物学概述,重点是ccRCC,以及更新,以补充当前的临床指南和RCC研究和治疗的潜在未来方向的大纲。
Renal cell carcinoma (RCC) denotes cancer originated from renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetics regulatory genes and demonstrated marked intratumour heterogeneity, which could have prognostic, predictive and therapeutic relevance. Localized RCC can be successfully managed with surgery whereas metastatic RCC is refractory to conventional chemotherapy. However, over the past decade, marked advances in treatment of metastatic RCC have been made, with targeted agents including sorafenib, sunitinib, bevacizumab, pazopanib and axitini that inhibit vascular endothelial growth factor (VEGF) and its receptor(VEGFR) and everolimus and temsirolimus, which inhibit mTOR complex 1, being approved. Since 2015, agents with additional targets aside from VEGFR have been approved, such as cabozantinib and lenvatinib; immunotherapies such as nivolumab have also been added to the armamentarium for metastatic RCC. Here, we provide an overview of the molecular biology of RCC, with a focus on ccRCC, as well as updates to complement current clinical guidelines and an outline of potential future directions for RCC research and therapy.
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