The School of Pharmaceutical Science, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, China.
Angiogenesis. 2012 Dec;15(4):521-42. doi: 10.1007/s10456-012-9295-8. Epub 2012 Aug 14.
Angiogenesis has emerged as a promising target of cancer treatment. With the development of biotechnology, major progress has been made in the exploring effective therapies on targeting tumor angiogenesis over the last 20 years. Gene therapy has attracted considerable interest by virtue of the capabilities of expressing sustained levels of therapeutic agents within cells of the patients. However, the major challenge of gene therapy is the efficient delivery of therapeutic gene to the target site. Compared with viral strategies, non-viral strategies were more acceptable by their widely recognized security and lower side effects. This paper reviews the basic biology of angiogenesis, the potential advantages of antiangiogenic gene therapy, the therapeutic genetic drugs developed through biotechnology, as well as the biotechnological strategies that enhancing non-viral gene therapy targeting to tumor angiogenesis in a more controlled manner, with great respect to RNA interference, ligand-directed vascular targeting strategies, vascular endothelial growth factor pathway and tumor associated macrophages targeting. In conclusion, antiangiogenic gene therapy holds great promise in advancing cancer therapy. Developing better non-viral biotechnological platforms will benefit antiangiogenic targeted cancer gene therapeutic methods, support their evaluation in human clinical trials and realize the actual utilization in the near future.
血管生成已成为癌症治疗的一个有前途的靶点。在过去的 20 年中,随着生物技术的发展,在探索针对肿瘤血管生成的有效治疗方法方面取得了重大进展。基因治疗因其能够在患者细胞内持续表达治疗剂的能力而引起了相当大的兴趣。然而,基因治疗的主要挑战是将治疗基因有效地递送到靶位。与病毒策略相比,非病毒策略因其广泛认可的安全性和较低的副作用而更被接受。本文综述了血管生成的基本生物学、抗血管生成基因治疗的潜在优势、通过生物技术开发的治疗性遗传药物,以及增强非病毒基因治疗靶向肿瘤血管生成的生物技术策略,更尊重 RNA 干扰、配体导向的血管靶向策略、血管内皮生长因子途径和肿瘤相关巨噬细胞靶向。总之,抗血管生成基因治疗在推进癌症治疗方面具有广阔的前景。开发更好的非病毒生物技术平台将有利于抗血管生成靶向癌症基因治疗方法,支持它们在人类临床试验中的评估,并在不久的将来实现实际应用。