Fudan University, Institute of Genetics, State Key Laboratory of Genetic Engineering, 220 Handan Road, Shanghai, 200433, P. R. China.
Expert Opin Ther Targets. 2011 Apr;15(4):421-37. doi: 10.1517/14728222.2011.555402. Epub 2011 Feb 21.
Integrins, which are heterodimeric membrane glycoproteins, consist of a family of cell-surface receptors mediating cell-matrix and cell-cell adhesion. Analysis of tumor-associated integrins has revealed an important relationship between integrins and tumor development, bringing new insights into integrin-based cancer therapies. Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide and integrins appeal to be a novel group of potential therapeutic targets for HCC.
This review summarizes the current knowledge of integrins involved in HCC and the potential of integrin-targeted drugs in HCC therapy. A brief introduction on the structure, biological function and regulatory mechanism of integrins is given. The distinct expression patterns and biological functions of HCC-associated integrins are described. Finally, the current situation of integrin-based therapies in HCC and other tumor types are extensively discussed in the light of their implications in preclinical and clinical trials.
To date, increasing numbers of integrin-targeted drugs are undergoing development and they exhibit diverse effects in cancer clinical trials. Tumor heterogeneity should be emphasized in developing effective integrin-targeted drugs specific for HCC. A better understanding of how integrins cooperatively function in HCC will assist in designing more successful integrin-targeted therapeutic drugs and corresponding approaches.
整合素是异二聚体膜糖蛋白,由介导细胞-基质和细胞-细胞黏附的细胞表面受体家族组成。对肿瘤相关整合素的分析揭示了整合素与肿瘤发展之间的重要关系,为基于整合素的癌症治疗带来了新的见解。肝细胞癌(HCC)是全球最恶性的肿瘤之一,整合素似乎是 HCC 的一组新的潜在治疗靶点。
本综述总结了参与 HCC 的整合素的最新知识,以及整合素靶向药物在 HCC 治疗中的潜力。简要介绍了整合素的结构、生物学功能和调节机制。描述了 HCC 相关整合素的独特表达模式和生物学功能。最后,根据临床前和临床试验中的意义,广泛讨论了基于整合素的治疗在 HCC 和其他肿瘤类型中的现状。
迄今为止,越来越多的整合素靶向药物正在开发中,它们在癌症临床试验中表现出不同的效果。在开发针对 HCC 的特异性有效整合素靶向药物时,应强调肿瘤异质性。更好地了解整合素在 HCC 中如何协同发挥作用,将有助于设计更成功的整合素靶向治疗药物和相应的方法。