Integrins: molecular targets in cancer therapy.
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.
Tucker
Gordon C
GC
Institut de Recherches Servier, Cancer Drug Discovery, 125 Chemin de Ronde, 78290 Croissy sur Seine, France. gordon.tucker@fr.netgrs.com
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000188:drug therapy; D002986:Clinical Trials as Topic; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D011166:Porphyrins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy; D012910:Snake Venoms / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D016023:Integrins; D011166:Porphyrins; D012910:Snake Venoms; D013449:Sulfonamides; C468872:N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzene-sulfonamide; C112567:etaracizumab; C422910:Cilengitide; C486839:intetumumab