Imiquimod as an antiangiogenic agent.
Imiquimod (imidazoquinoline 5%) is a topical immune response modifier agent that inhibits angiogenesis, the growth of new blood vessels. In addition to its stimulation of cell-mediated immunity, imiquimod's antiangiogenic activity contributes to its clinical efficacy by interfering with pathological neovascularization that promotes disease progression. The antiangiogenic mechanisms of imiquimod are due to its: 1) induction of cytokines that themselves inhibit angiogenesis (interferons, IL-10, IL-12); 2) local up-regulation of endogenous angiogenesis inhibitors (TIMP, TSP-1); 3) local down-regulation of pro-angiogenic factors (bFGF, MMP-9); and 4) promotion of endothelial cell apoptosis. This report discusses these mechanisms and the rationale for imiquimod's use as an antiangiogenic agent. Key principles of antiangiogenic therapy are presented to describe how imiquimod may be applied in a well-tolerated fashion to treat a broad range of angiogenesis-dependent dermatological conditions, including actinic keratosis (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), lentigo maligna, hemangiomas, Kaposi's sarcoma, pyogenic granuloma, and external genital warts.
Li
Vincent W
VW
The Angiogenesis Foundation, Cambridge, MA 02238, USA. vli@angio.org
Li
William W
WW
Talcott
Katherine E
KE
Zhai
Amy W
AW
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use; D000634:Aminoquinolines / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use*; D020533:Angiogenesis Inhibitors / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000077271:Imiquimod; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D019700:Thrombospondin 1 / Q000187:drug effects / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D020533:Angiogenesis Inhibitors; D016207:Cytokines; D019700:Thrombospondin 1; D019714:Tissue Inhibitor of Metalloproteinases; D016222:Fibroblast Growth Factor 2; D020780:Matrix Metalloproteinase 9; D000077271:Imiquimod