Integrin α6: a potential target for cancer molecular imaging and targeting therapy

Xin-Ling Li, Zhuo-Lun Shen, Qiao-Li Wang, Jia-Cong Ye, Wen-Biao Zhang, Ying-He Li, Guo-Kai Feng, Mu-Sheng Zeng
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Abstract

As a major kind of cell surface adhesion molecules with signal transduction function, integrins play a major role in tumorigenesis and tumor progression. The role of integrins in tumor cells and the tumor microenvironment has been extensively revealed. Among the integrin family, integrin αvβ3 is the most studied integrin in the past 20 years. Plenty of preclinical and clinical studies have been conducted, which showed clinical benefits of targeting integrin αvβ3 in tumor imaging and treatment. Currently, the focus of interest is gradually shifting from integrin αvβ3 toward other integrin subtypes. Integrin α6 is expressed in many malignant tumors, such as colorectal cancer, head and neck squamous cell carcinoma, breast cancer, pancreatic cancer, and liver cancer, and its expression is correlated with poor survival of the patients. Recent studies have shown that tumor molecular imaging agents and therapeutic drugs targeting integrin α6 have excellent safety and efficacy in preclinical mouse models, encouraging clinical translation of this promising target. In this review, we briefly overview the physiological and pathological function of integrin α6 and highlight the recent advances in integrin α6-targeted imaging and therapeutics in tumors.

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整合素α6:癌症分子成像和靶向治疗的潜在靶点
整合素作为一种主要的细胞表面粘附分子,具有信号转导功能,在肿瘤发生和发展过程中发挥着重要作用。整合素在肿瘤细胞和肿瘤微环境中的作用已被广泛揭示。在整合素家族中,整合素αvβ3是近20年来研究最多的整合素。大量临床前和临床研究表明,以整合素αvβ3 为靶点的肿瘤成像和治疗具有临床疗效。目前,人们关注的焦点正逐渐从整合素αvβ3转向其他整合素亚型。整合素α6在结直肠癌、头颈部鳞状细胞癌、乳腺癌、胰腺癌和肝癌等多种恶性肿瘤中均有表达,且其表达与患者的不良生存率相关。最近的研究表明,以整合素α6 为靶点的肿瘤分子成像剂和治疗药物在临床前小鼠模型中具有极佳的安全性和有效性,这鼓励了这一有前景靶点的临床转化。在这篇综述中,我们将简要概述整合素α6的生理和病理功能,并重点介绍整合素α6靶向肿瘤成像和治疗的最新进展。
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