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Abstract：
Integrins have been extensively investigated as therapeutic targets over the last decades, which has been inspired by their multiple functions in cancer progression, metastasis, and angiogenesis as well as a continuously expanding number of other diseases, e.g., sepsis, fibrosis, and viral infections, possibly also Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Although integrin-targeted (cancer) therapy trials did not meet the high expectations yet, integrins are still valid and promising targets due to their elevated expression and surface accessibility on diseased cells. Thus, for the future successful clinical translation of integrin-targeted compounds, revisited and innovative treatment strategies have to be explored based on accumulated knowledge of integrin biology. For this, refined approaches are demanded aiming at alternative and improved preclinical models, optimized selectivity and pharmacological properties of integrin ligands, as well as more sophisticated treatment protocols considering dose fine-tuning of compounds. Moreover, integrin ligands exert high accuracy in disease monitoring as diagnostic molecular imaging tools, enabling patient selection for individualized integrin-targeted therapy. The present review comprehensively analyzes the state-of-the-art knowledge on the roles of RGD-binding integrin subtypes in cancer and non-cancerous diseases and outlines the latest achievements in the design and development of synthetic ligands and their application in biomedical, translational, and molecular imaging approaches. Indeed, substantial progress has already been made, including advanced ligand designs, numerous elaborated pre-clinical and first-in-human studies, while the discovery of novel applications for integrin ligands remains to be explored.
摘要：
在过去的几十年中，整合素作为治疗靶点被广泛研究。这受到了它们在癌症进展中的多种功能的启发，转移,血管生成以及数量不断扩大的其他疾病，例如，脓毒症,纤维化，和病毒感染，也可能是严重急性呼吸系统综合症冠状病毒（SARS-CoV-2）。尽管整合素靶向（癌症）治疗试验尚未达到高期望，整合素由于其在病变细胞上的表达和表面可及性升高，仍然是有效和有希望的靶标。因此，对于未来整合素靶向化合物的成功临床翻译，必须根据整合蛋白生物学的积累知识来探索重新审视和创新的治疗策略。为此，需要针对替代和改进的临床前模型的改进方法，优化整合素配体的选择性和药理学性质，以及考虑到化合物剂量微调的更复杂的治疗方案。此外，整合素配体作为诊断分子成像工具在疾病监测中具有很高的准确性，使患者能够选择个体化的整合素靶向治疗。本综述全面分析了RGD结合整合素亚型在癌症和非癌症疾病中的作用，并概述了合成配体的设计和开发及其在生物医学中的应用的最新成就，翻译,和分子成像方法。的确,已经取得了实质性进展，包括先进的配体设计，许多精心阐述的临床前和人体首次研究，而整合素配体的新应用的发现仍有待探索。
