Title:CXCR4 Inhibitors: Tumor Vasculature and Therapeutic Challenges
Volume: 7
Issue: 3
Author(s): Filomena de Nigris, Concetta Schiano, Teresa Infante and Claudio Napoli
Affiliation:
Keywords:
Angiogenesis, cancer, CXCL12, CXCR4, metastasis, vasculogenesis, CCX2066 (ChemoCentryx), multiple myeloma, leukaemia, chronic lymphatic leukaemia treatment
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.
