Topical Imiquimod
Imiquimod belongs to the family of synthetic small nucleotid-like molecules of imidazo-quinolinamines. It is an immune response modifier (IRM) with potent antiviral and antitumoral effects that are mediated through Toll-like receptor (TLR)7 (and 8) signal
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Lajos Kemény
Key Points
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Imiquimod belongs to the family of synthetic small nucleotid-like molecules of imidazoquinolinamines. It is an immune response modifier (IRM) with potent antiviral and antitumoral effects that are mediated through Toll-like receptor (TLR)7 (and 8) signaling. Imiquimod targets predominantly TLR7 expressing plasmacytoid dendritic cells (pDC) and Langerhans cells, with secondary recruitment and activation of other inflammatory cells. Activation of TLR7 results therefore in the stimulation of both the innate and acquired immune responses, in particular, cell-mediated immune pathways. Topical imiquimod cream 5% (Aldara™, 3M) has been found to be effective for the treatment of external genital and perianal warts, actinic keratoses (AK), and superficial basal cell carcinoma (sBCC) in immunocompetent adults. There are some data on its efficacy in nodular BCC (nBCC) and in some other skin cancers.
15.1 Introduction The immune system plays an important role in the pathogenesis of nonmelanoma skin cancer (NMSC). Immunosuppressed patients, such as organ-transplant recipients, have a greater incidence of squamous cell carcinomas (SCC); their preinvasive form, actinic keratoses (AK); basal cell carcinomas (BCC); and other skin tumors [7, 12, 43]. Since the cellular immune response plays a role in suppressing the development and growth of cancers, it is not too outrageous that an immune response modifier such as imiquimod could be used to treat cancers. Topical imiquimod cream 5% (Aldara™, 3M) is a topical immune response modifier (IRM) that enhances both the innate and acquired immune responses, in particular, the cell-mediated immune pathways (Fig. 15.1). Imiquimod has been approved for the treatment of external genital and perianal warts, actinic keratoses (AK), and superficial basal cell carcinoma (sBCC) in immunocompetent adults. There are some data on its efficacy in nodular BCC (nBCC) and in some other types of cutaneous malignancies. In this chapter, the current experience and possible future development of imiquimod for the treatment of NMSC are reviewed.
15.2 Mechanism of Action L. Kemény Department of Dermatology and Allergology, University of Szeged, Hungary e-mail: [email protected]
Imiquimod belongs to the family of synthetic small nucleotid-like molecules of imidazoquinolinamines. It is an immune response modifier (IRM) with potent antiviral and antitumoral effects.
G. B. E. Jemec et al. (eds.), Non-Surgical Treatment of Keratinocyte Skin Cancer, DOI: 10.1007/978-3-540-79341-0_15, © Springer-Verlag Berlin Heidelberg 2010
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Fig. 15.1 Effects of imiquimod on the innate and acquired immunity
Imiquimod exerts its biologic activity primarily by ligation of Toll-like receptor (TLR)7 and, to a lesser extent, TLR8, both of which have been identified as natural receptors for single-stranded RNA [3, 11, 19]. Cell stimulation via TLR7 and TLR8 leads to downstream activation of nuclear factor (NF)-kB and other transcription factors [4, 29]. Conse
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