Targeting the integrin interactome in human disease

Integrins comprise one of the most important families of cell–cell or cell–matrix adhesion receptors. Integrin interaction with their extracellular ligands is tunable by microenvironment signals, such as chemokines and growth factors, which modulate their interaction with other transmembrane proteins and cytoplasmic interactors. Integrins are important in different disease contexts, particularly inflammatory diseases and cancer. Clinical trials targeting integrins began in the early 2000s, leading to an increasingly clear picture: agents against integrins and their interactome control inflammatory diseases; whereas their efficacy as anti-cancer targets remains dubious. Here, we discuss the success of integrin targeting to treat autoimmunity and its failure in cancer, which is rooted in the plasticity and adaptability of the cancer cell.