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靶向血管生成基因作为肝细胞癌的一种治疗方法。

Targeting angiogenic genes as a therapeutic approach for hepatocellular carcinoma.

作者信息

Wong Chi Hang, Wong Cesar S C, Chan Stephen L

机构信息

Department of Clinical Oncology, The Chinese University of Hong Kong.

出版信息

Curr Gene Ther. 2015;15(2):97-108. doi: 10.2174/1566523214666141224094648.

Abstract

Hepatocellular carcinoma (HCC) is a complex liver disease with limited treatment options and often resulting in a poor prognosis. The development of HCC depends on the formation of new blood vessels and it demonstrates hypervascularity and invasive property to the surrounding vasculature clinically. A complex network of growth factors acting on both tumor cells and endothelial cells mediates the angiogenesis in HCC. It is an attractive approach to inhibit the angiogenic processes as the treatment of HCC and therefore, anti-angiogenic TKIs were developed to inhibit the vessel formation in the tumors. However, it is currently perceived that the efficacy of these anti-angiogenic TKIs has reached plateau, and it is necessary to develop novel agents with non-TKI mechanism to inhibit the angiogenic targets. With the better understanding of molecular mechanisms that govern angiogenesis, as well as the advancement in biomedical engineering, new approaches of gene therapy have brought hopes for therapeutic intervention in HCC. Gene therapy is based on the transfer of genetic material to the patients with the aim to modify or correct the malignancy from its molecular basis. In this article, we will discuss the conventional anti-angiogenic therapies and the gene therapy approaches in HCC. The therapeutic potential of gene therapy for HCC treatment has been demonstrated and further development of anti-angiogenic may result in new treatment option for HCC patients.

摘要

肝细胞癌(HCC)是一种复杂的肝脏疾病,治疗选择有限,预后往往较差。HCC的发展依赖于新血管的形成,临床上表现为血管丰富且对周围血管具有侵袭性。作用于肿瘤细胞和内皮细胞的复杂生长因子网络介导了HCC中的血管生成。抑制血管生成过程作为HCC的治疗方法是一种有吸引力的途径,因此,开发了抗血管生成酪氨酸激酶抑制剂(TKIs)来抑制肿瘤中的血管形成。然而,目前认为这些抗血管生成TKIs的疗效已达到平台期,有必要开发具有非TKI机制的新型药物来抑制血管生成靶点。随着对血管生成分子机制的深入了解以及生物医学工程的进步,基因治疗的新方法为HCC的治疗干预带来了希望。基因治疗基于将遗传物质转移给患者,旨在从分子基础上改变或纠正恶性肿瘤。在本文中,我们将讨论HCC中的传统抗血管生成疗法和基因治疗方法。基因治疗对HCC治疗的潜在疗效已得到证实,抗血管生成的进一步发展可能为HCC患者带来新的治疗选择。

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