title: CXCR4 inhibitors: tumor vasculature and therapeutic challenges.
abstract: CXCL12, also known as SDF-1, is the single natural ligand for chemokine receptors CXCR4 and CXCR7. CXCL12 has angiogenic properties in normal endothelial tissue and is involved in the outgrowth and metastasis of CXCR4 expressing tumors. Recent investigations have indicated that CXCL12 levels increase after chemo- and anti- VEGF therapy, favouring recurrences. The blockade of CXCL12/CXCR4 axis has emerged as a potential additional or alternative target for neo-adjuvant treatments. We have reviewed recent patent applications between 2008 and 2011 in tumor angiogenesis and the most clinical data supporting the potential use of anti-CXCR4 agents in this field. Among these, AMD3100, also known as Plerixaform (Mozobil by Genzyme), is approved for stem cell mobilisation in patients with leukaemia, while BKT140 (Emory University), POL6326 (Polyphor Ag) and TG-0054 (ChemoCentryx) are currently in clinical trials in combination with chemotherapy for multiple myeloma and leukaemia. The aptamer Nox-A12 (Noxxon) is in trials for chronic lymphatic leukaemia treatment. MSX-122 (Metastatix) is in Phase I trials for solid tumor treatment, while CXCR7-specific inhibitor CCX2066 (ChemoCentryx) is still in preclinical studies. We have also considered other strategies, such RNA interference and miRNA, which could be tested for solid tumor adjuvant therapy.
authors.affiliation: Department of General Pathology and Excellence Research Centre on Cardiovascular Diseases, 1st School of Medicine, Second University of Naples, Complesso S. Andrea delle Dame, Via Costantinopoli 16, Naples, 80138, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: de Nigris
authors.forename: Concetta
authors.initials: C
authors.lastname: Schiano
authors.forename: Teresa
authors.initials: T
authors.lastname: Infante
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4