Department of Cellular Pharmacology - Oncology Platform, Merck KGaA, Frankfurterstrasse 250, 64271 Darmstadt, Germany.
Trends Pharmacol Sci. 2012 Jul;33(7):405-12. doi: 10.1016/j.tips.2012.04.002. Epub 2012 May 25.
Integrins are a large family of molecules that are central regulators in multicellular biology. They orchestrate cell-cell and cell-extracellular matrix (ECM) adhesive interactions from embryonic development to mature tissue function. Diverse human pathologies involve integrin adhesion, including thrombotic diseases, inflammation, cancer, fibrosis and infectious diseases. Integrins are exciting pharmacological targets because they are exposed on the cell surface and are sensitive to pharmacological blockade, but the scale of current efforts involving integrin therapeutics continues to surprise. Several therapeutics targeting integrins are effective drugs: five have been approved for use in clinic, with combined sales of over $1.5 billion in 2010 (based on company reports from that year). We gathered information from three major drug-trial databases and found that ∼260 anti-integrin drugs have entered clinical trials. Here we overview integrins as drug targets and focus on cancer.
整合素是一大类分子，它们是多细胞生物学中的核心调节剂。它们从胚胎发育到成熟组织功能，协调细胞-细胞和细胞-细胞外基质（ECM）的黏附相互作用。多种人类病理涉及整合素黏附，包括血栓性疾病、炎症、癌症、纤维化和传染病。整合素是令人兴奋的药物靶点，因为它们暴露在细胞表面，对药物阻断敏感，但涉及整合素治疗的当前努力的规模仍然令人惊讶。几种针对整合素的治疗方法是有效的药物：五种已被批准用于临床，2010 年的销售额超过 15 亿美元（基于当年公司报告）。我们从三个主要的药物试验数据库中收集信息，发现约有 260 种抗整合素药物已进入临床试验。在这里，我们将整合素作为药物靶点进行综述，并重点介绍癌症。
