PDF(Pubmed)
Abstract：
A relevant challenge for the treatment of patients with neoplasia is the development of resistance to chemo-, immune-, and radiotherapies. Although the causes of therapy resistance are poorly understood, evidence suggests it relies on compensatory mechanisms that cells develop to replace specific intracellular signaling that should be inactive after pharmacological inhibition. One such mechanism involves integrins, membrane receptors that connect cells to the extracellular matrix and have a crucial role in cell migration. The blockage of one specific type of integrin is frequently compensated by the overexpression of another integrin dimer, generally supporting cell adhesion and migration. In particular, integrin αvβ3 is a key receptor involved in tumor resistance to treatments with tyrosine kinase inhibitors, immune checkpoint inhibitors, and radiotherapy; however, the specific inhibition of the αvβ3 integrin is not enough to avoid tumor relapse. Here, we review the role of integrin αvβ3 in tumor resistance to therapy and the mechanisms that have been proposed thus far. Despite our focus on the αvβ3 integrin, it is important to note that other integrins have also been implicated in drug resistance and that the collaborative action between these receptors should not be neglected.
摘要：
治疗肿瘤患者的一个相关挑战是对化疗的耐药性的发展。免疫-，和放射治疗。尽管人们对治疗抵抗的原因知之甚少，有证据表明，它依赖于代偿机制，即细胞发育以取代特定的细胞内信号，这些信号在药物抑制后应该是无活性的。其中一种机制涉及整合素，连接细胞与细胞外基质并在细胞迁移中起关键作用的膜受体。一种特定类型的整合素的阻断通常由另一种整合素二聚体的过表达来补偿。通常支持细胞粘附和迁移。特别是,整合素αvβ3是参与肿瘤对酪氨酸激酶抑制剂治疗耐药的关键受体，免疫检查点抑制剂，和放射治疗；然而，αvβ3整联蛋白的特异性抑制不足以避免肿瘤复发。这里,我们回顾了整合素αvβ3在肿瘤对治疗的抵抗中的作用以及迄今为止已经提出的机制。尽管我们关注的是αvβ3整合素,值得注意的是，其他整合素也与耐药性有关，这些受体之间的协同作用不可忽视。
