Integrins: molecular targets in cancer therapy

Abstract

Integrins are cell surface adhesion molecules coupling the extracellular environment to the cytoskeleton as well as receptors for transmitting signals important for cell migration, invasion, proliferation, and survival. At least six integrin inhibitors are being evaluated in clinical trials for cancer. Currently, patients with melanoma and glioblastoma multiforme benefit from Vitaxin (MedImmune, Gaithersburg, MD) or cilengitide treatment, respectively. Many phase II trials are being or have been conducted with these two compounds (the most advanced). Surprisingly, despite the broad theoretical impact of such molecules on integrin function, and thus on pathology, the clear identification of discrete clinical niches for their use remains to be defined. Possible reasons for this are discussed in this review. The parallel development of integrin antagonists as imaging tools for patient selection may accelerate the discovery of new avenues for their use.