Strategies To Inhibit Tumor Associated Integrin Receptors: Rationale for Dual and Multi-Antagonists
Strategies To Inhibit Tumor Associated Integrin Receptors: Rationale for Dual and Multi-Antagonists
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DOI：
10.1021/jm5000547
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发表时间：
2014-08-14
影响因子：
7.3
通讯作者：
Patterson, Laurence H.
中科院分区：
文献类型：
--
作者：
Sheldrake, Helen M.;Patterson, Laurence H.
整联蛋白是一个由24个异二聚体跨膜细胞表面受体组成的家族。整合素参与细胞与细胞外基质的附着、运动和增殖，从而确定了整合素作为癌症和相关病症（血栓形成、血管生成和骨质疏松症）中的治疗靶点。报道最多的药物开发策略是合成一种对单一整联蛋白受体具有高度选择性的药物。然而，癌细胞响应于药物治疗而改变其整联蛋白库的能力使得这种方法容易产生耐药性和矛盾地促进肿瘤生长。在此，我们综述了针对Arg-Gly-Asp（RGD）结合整联蛋白的两个或多个成员的拮抗剂的开发进展，特别是α（v）β（3），α（v）β（s），α（v）β（6），α（v）β（8），α（s）β（1）和α（IIb）β（3）作为抗癌治疗剂。
The integrins are a family of 24 heterodimeric transmembrane cell surface receptors. Involvement in cell attachment to the extracellular matrix, motility, and proliferation identifies integrins as therapeutic targets in cancer and associated conditions: thrombosis, angiogenesis, and osteoporosis. The most reported strategy for drug development is synthesis of an agent that is highly selective for a single integrin receptor. However, the ability of cancer cells to change their integrin repertoire in response to drug treatment renders this approach vulnerable to the development of resistance and paradoxical promotion of tumor growth. Here, we review progress toward development of antagonists targeting two or more members of the Arg-Gly-Asp (RGD) binding integrins, notably alpha(v)beta(3), alpha(v)beta(s), alpha(v)beta(6), alpha(v)beta(8), alpha(s)beta(1), and alpha(IIb)beta(3) as anticancer therapeutics.