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Integrins are the main cell adhesion mediators on the cell surface. Especially integrin α v β 3 has gained a lot of attention as a target in cancer therapy because it mediates diverse angiogenic processes during tumor development. The peptide sequence Arg-Gly-Asp (RGD), which is present in a number of endogenous integrin ligands like fibronectin, vitronectin, and related proteins of the extracellular matrix (ECM), has been extensively used as a targeting vector for therapeutic as well as diagnostic purposes, and cilengitide, a cyclic RGD peptide, has entered clinical trials for the treatment of various cancers. However, recent advancements utilizing isoDGR, a sequence that was found in aged fibronectin, already show that RGD-based targeting is not the end of the line. Novel developments and a closer investigation of the binding mode of these peptides now show promising results for the future use of such compounds.

isoDGR-Peptides for Integrin Targeting: Is the Time Up for RGD?