title: The CXCL12/CXCR4 axis as a therapeutic target in cancer and HIV-1 infection.
abstract: The seven-spanning transmembrane G-protein coupled receptor CXCR4, which specifically binds to the chemokine CXCL12, is expressed on many cell types, including various types of tumour cells. CXCR4 plays a crucial role in organ-specific metastasis, directing migration of malignant cells expressing this receptor toward microenvironments where the cognate ligand is secreted. CXCL12 has a direct growth and survival-promoting effect for various cancer cells and enhances moreover tumour angiogenesis by recruiting endothelial progenitor cells to tumours. Drugs which modulate the CXCL12/CXCR4 axis are therefore promising candidates in anti-cancer therapies. CXCR4 is also a coreceptor for human immunodeficiency virus type 1 (HIV-1) X4 virus and, as such, plays an important role in virus entry into target cells. Hence, antiviral agents that bind to CXCR4 are expected to inhibit HIV-1 entry. Here we review the structure, mechanism of action and biological activity of the main CXCR4 antagonists (peptide inhibitors, non-peptide antagonists, neutralizing antibodies, modified analogues of CXCL12) and agonists (CXCL12 peptide analogues) and discuss the CXCL12/CXCR4 axis as an important target in development of anti-tumoral and anti-HIV-1 therapies.
authors.affiliation: Department of Evolutionary Biology, University of Siena, Via Aldo Moro 2, 53100 Siena, Itlay. patrussi2@unisi.it
authors.forename: L
authors.initials: L
authors.lastname: Patrussi
authors.forename: C T
authors.initials: CT
authors.lastname: Baldari
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D054377:Chemokine CXCL12 / Q000819:agonists* / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use; D019718:Receptors, CXCR4 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D054377:Chemokine CXCL12; D010455:Peptides; D019718:Receptors, CXCR4; D054852:Small Molecule Libraries