The challenges and opportunities of alpha v beta 3-based therapeutics in cancer: From bench to clinical trials

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 alpha v beta 3 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 alpha v beta 3 was associated with various tumor progressions, including tumor initiation, sustained tumor growth, distant metastasis, drug resis-tance development, maintenance of stemness in cancer cells. Therefore, alpha v beta 3 has been explored as a therapeutic target in various types of cancers, but there is no alpha v beta 3 antagonist approved for human therapy. Targeting-integrin alpha v beta 3 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 alpha v beta 3, and also provided new insights into alpha v beta 3-based therapeutics in cancer from bench to clinical trials, which would contribute to developing effective targeting alpha v beta 3 agents for cancer treatment.