整合素是主要的细胞粘附受体，作为连接细胞与细胞外基质（ECM）的链接器，以及在细胞与环境之间传递生化和机械信号的双向枢纽。整合素αvβ3是整合素家族的关键成员，与包含RGD三肽序列的ECM蛋白相互作用。越来越多的证据表明，整合素αvβ3的异常表达与各种肿瘤进展有关，包括肿瘤起始、持续生长、远处转移、耐药性发展、维持癌细胞干性等。因此，αvβ3已成为各种癌症治疗的治疗靶点，但尚未批准任何αvβ3拮抗剂用于人体疗法。靶向整合素αvβ3治疗一直是一个挑战，但过去的经验对开发创新的靶向方法具有价值。本综述系统总结了整合素αvβ3的结构、信号转导、在癌症中的调节作用和药物开发历史，并提供了关于从实验室到临床试验的αvβ3基础治疗学的新见解，这将有助于开发有效的靶向αvβ3剂量，用于癌症治疗。版权©2023作者。由Elsevier Ltd.发表。保留所有权利。

Integrins are main cell adhesion receptors serving as linker attaching cells to extracellular matrix (ECM) and bidirectional hubs transmitting biochemical and mechanical signals between cells and their environment. Integrin αvβ3 is a critical family member of integrins and interacts with ECM proteins containing RGD tripeptide sequence. Accumulating evidence indicated that the abnormal expression of integrin αvβ3 was associated with various tumor progressions, including tumor initiation, sustained tumor growth, distant metastasis, drug resistance development, maintenance of stemness in cancer cells. Therefore, αvβ3 has been explored as a therapeutic target in various types of cancers, but there is no αvβ3 antagonist approved for human therapy. Targeting-integrin αvβ3 therapeutics has been a challenge, but lessons from the past are valuable to the development of innovative targeting approaches. This review systematically summarized the structure, signal transduction, regulatory role in cancer, and drug development history of integrin αvβ3, and also provided new insights into αvβ3-based therapeutics in cancer from bench to clinical trials, which would contribute to developing effective targeting αvβ3 agents for cancer treatment.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.