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我们能否为肝细胞癌患者开发有效的联合抗血管生成疗法?

Can we develop effective combination antiangiogenic therapy for patients with hepatocellular carcinoma?

作者信息

Wenger Justin B, Santos Napoleon, Liu Yanxia, Dallas Jennifer, Subbiah Sukanthini, Hochwald Steven, Huang Emina H, Dang Duyen T, Allegra Carmen J, Luesch Hendrik, Dang Long H

机构信息

Division of Hematology/Oncology, Department of Internal Medicine, University of Florida Shands Cancer Center, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.

出版信息

Oncol Rev. 2011 Sep;5(3):177-184. doi: 10.1007/s12156-011-0082-3.

DOI:10.1007/s12156-011-0082-3
PMID:21949574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3179415/
Abstract

Antiangiogenic therapy has shown promise in the treatment of patients with hepatocellular carcinoma (HCC). Bevacizumab, sorafenib, and sunitinib showed efficacy in patients with HCC; and sorafenib is approved by the FDA for treatment of this cancer. In practice, the clinical benefit of these agents has been heterogeneous; and in patients who do respond, the benefit is modest and/or short-lived. Recent advances in the molecular understanding of tumor angiogenesis along with the rapid development of targeted drug discovery have made it possible to explore novel combination therapy for HCC. We review the clinical trial results, discuss possible molecular mechanisms of resistance, and suggest novel combinations with antiangiogenic therapy.

摘要

抗血管生成疗法在肝细胞癌(HCC)患者的治疗中已显示出前景。贝伐单抗、索拉非尼和舒尼替尼在HCC患者中显示出疗效;并且索拉非尼已获得美国食品药品监督管理局(FDA)批准用于治疗这种癌症。在实际应用中,这些药物的临床获益存在异质性;而且在有反应的患者中,获益程度不大和/或持续时间较短。肿瘤血管生成分子认识方面的最新进展以及靶向药物研发的快速发展使得探索HCC的新型联合治疗成为可能。我们回顾了临床试验结果,讨论了可能的耐药分子机制,并提出了抗血管生成疗法的新型联合方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f20/4525808/f7db242bfad5/12156_2011_82_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f20/4525808/f7db242bfad5/12156_2011_82_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f20/4525808/f7db242bfad5/12156_2011_82_Fig1_HTML.jpg

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本文引用的文献

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Oncogenic KRAS modulates mitochondrial metabolism in human colon cancer cells by inducing HIF-1α and HIF-2α target genes.致癌性 KRAS 通过诱导 HIF-1α 和 HIF-2α 靶基因来调节人结肠癌细胞中的线粒体代谢。
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Hypoxia-inducible factor-1 alpha, in association with inflammation, angiogenesis and MYC, is a critical prognostic factor in patients with HCC after surgery.缺氧诱导因子-1α与炎症、血管生成和 MYC 相关,是 HCC 患者手术后的一个关键预后因素。
BMC Cancer. 2009 Dec 1;9:418. doi: 10.1186/1471-2407-9-418.
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Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics.定义缺氧诱导因子 1 在癌症生物学和治疗学中的作用。
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