134
Views
24
CrossRef citations to date
0
Altmetric
Review

The small-molecule immune response modifier imiquimod – its mode of action and clinical use in the treatment of skin cancer

&
Pages 69-76 | Published online: 27 Jan 2006

Bibliography

  • CHANG AE, KARNELL LH, MENCK HR: The national cancer database report of cutaneous and noncutaneous melanoma. Cancer (1998) 78:1664-1668.
  • ARMSTRONG BK, KRICKER A: Cutaneous melanoma. Cancer Surveys (1994) 19:219-240.
  • BECKER JC, KÄMPGEN E, BRÖCKER EB: Classical chemotherapy for metastatic melanoma. Clin. Exp. Dermatol. (2000) 25:503-508.
  • SCHNEEBERGER A, GOOS M, STINGL G, WAGNER SN: Management of malignant melanoma: new developments in immune and gene therapy. Clin. Exp. Dermatol. (2000) 25:509-519.
  • HUSSEIN MR, HAEMEL AK, WOOD GS: Apoptosis and melanoma: molecular mechanisms. J. Pathol. (2003) 199:275-288.
  • ARIZA ME, BROOME-POWELL M, LAHTI JM, KIDD VJ, NELSON MA: Fas-induced apoptosis in human malignant melanoma cell lines is associated with the activation of the p34(cdc2)-related PITSLRE protein kinases. J. Biol. Chem. (1999) 274:28505-28513.
  • BAYAERT R, KIDD VJ, CORNELIS S et al.: Cleavage of PITSLRE kinases by ICE/CASP-1 and CPP32/CASP-3 during apoptosis induced by tumor necrosis factor. J. Biol. Chem. (1997) 272:11694-11697.
  • NELSON MA, ARIZA ME, YANG JM et al.: Abnormalities in the p34cdc2-related PITSLRE protein kinase gene complex (CDC2L) on chromosome band 1p36 in melanoma. Cancer Genet. Cytogenet. (1999) 108:91-99.
  • GRIFFITH TS, CHIN WA, JACKSON GC, LYNCH DH, KUBIN MZ: Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. J. Immunol. (1998) 161:2833-2840.
  • FRANCO AV, ZHANG XD, VAN BERKEL E et al.: The role of NF-κB in TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of malignant melanoma. J. Immunol. (2001) 166:5337-5345.
  • URQUHART JL, MEECH SJ, MARR DG, SHELLMAN YG, DUKE RC, NORRIS DA: Regulation of Fas-mediated apoptosis by N-ras in melanoma. J. Invest. Dermatol. (2002) 119:556-561.
  • UGUREL S, SEITER S, RAPPL G, STARK A, TILGEN W, REINHOLD U: Heterogenous susceptibility to CD95-induced apoptosis in melanoma cells correlates with bcl-2 and bcl-X expression and is sensitive to modulation by interferon-gamma. Int. J. Cancer (1999) 82:727-736.
  • ZHANG XD, FRANCO AV, NGUYEN T, GRAY CP, HERSEY P: Differential localization and regulation of death and decoy receptors for TNF-related apoptosis-inducing ligand (TRAIL) in human melanoma cells. J. Immunol. (2000) 164:3961-3970.
  • SHIN MS, PARK WS, KIM SY et al.: Alterations of Fas (Apo-1/CD95) gene in cutaneous malignant melanoma. Am. J. Pathol. (1999) 154:1785-1791.
  • HELMBACH H, SINHA P, SCHADENDORF D: Human melanoma: drug resistance. Recent Results Cancer Res. (2003) 161:93-110.
  • KAUFMANN SH, EARNSHAW WC: Induction of apoptosis by cancer chemotherapy. Exp. Cell. Res. (2000) 256:42-49.
  • GALLAGHER RP, MA B, MCLEAN DI: Trends in basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin from 1973 through 1987. J. Am. Acad. Dermatol. (1990) 23:413-421.
  • GILES GG, MARKS R, FOLEY P: The incidence of nonmelanoma skin cancer treated in Australia. Br. Med. J. (1988) 296:13-17.
  • GOLDBERG LH: Basal cell carcinoma. Lancet (1996) 347:663-666.
  • MARKS R: Squamous cell carcinoma. Lancet (1996) 347:735.
  • PRESTON DS, STERN RS: Nonmelanoma skin cancers of the skin. N. Engl. J. Med. (1992) 327:1649-1662.
  • MCKEE RM: Epidermal skin tumors. In: Textbook of Dermatology, RH Champion, JL Burton, DA Burns and SM Breathnach, Eds., Blackwell Science, New York (1998):1656-1687.
  • MARKS R: Nonmelanotic skin cancer and solar keratoses, the quiet 20th century epidemic. Int. J. Dermatol. (1987) 26:201-205.
  • CLEAVER JE, BOOTSMA D: Xeroderma pigmentosum: biochemical and genetic characteristics. Ann. Rev. Genet. (1975) 9:19-38.
  • CLENDENNING WE, BLOCK JB, RADDE JG: Basal cell nevus syndrome. Arch. Dermatol. (1964) 90:38-53.
  • GAILANI MR, STAHLE-BÄCKDAHL M, LEFFELL DJ: The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat. Genet. (1996) 14:78-81.
  • HAHN H, WICKING C, ZAPHIROPOULOS PG: Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell (1996) 85:841-851.
  • LEAR JT, HEAGERTY AHM, SMITH A: Multiple cutaneous basal cell carcinomas: glutathione S-transferase (GSTM1, GSTT1) and cytochrome P450 (CYP2D6, CYP1A1) polymorphisms influence tumor numbers and accural. Carcinogenesis (1996) 17:1891-1896.
  • WOLTER M, REIFENBERGER J, SOMMER C, RUZICKA T, REIFENBERGER G: Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res. (1997) 57:2581-2585.
  • ZIEGLER A, JONASON AS, LEFFELL DJ et al.: Sunburn and p53 in the onset of skin cancer. Nature (1994) 372:773-776.
  • DAZARD JE, GAL H, AMARIGLIO N, RECHAVI G, DOMANY E, GIVOL D: Genome-wide comparison of human keratinocyte and squamous cell carcinoma responses to UVB irradiation: implications for skin and epithelial cancer. Oncogene (2003) 22:2993-3006.
  • POPP S, WALTERING S, HERBST C, MOLL I, BOUKAMP P: UV-B-type mutations and chromosomal imbalances indicate common pathways for the development of Merkel and skin squamous cell carcinomas. Int. J. Cancer (2002) 99:352-360.
  • THOMPSON CB: Apoptosis in the pathogenesis and treatment of disease. Science (1995) 267:1456-1462.
  • CALLEN JP: Possible precursors to epidermal malignancies. In: Cancer of the Skin, RB Friedman, DS Rigel, AW Kopf, MN Harris, D Baker, Eds., Saunders, New York. (1991):27-30.
  • WALDER BK, ROBERTSON MR, JEREMY DR: Skin cancer and immunosuppression. Lancet (1971) 2:1282-1283.
  • KURWA HA, MARKS R: Protracted cutaneous disorders in association with low CD4+ lymphocyte counts. Br. J. Dermatol. (1995) 133:625-629.
  • SITZ KV, KEPPEN M, JOHNSON DF: Metastatic basal cell carcinoma in acquired immunodeficiency syndrome-related complex. JAMA (1987) 257:340-343.
  • SCHÖN MP, REIFENBERGER J, VON SCHMIEDEBERG S et al.: Multiple basal cell carcinomas associated with hairy cell leukemia. Br. J. Dermatol. (1999) 140:150-153.
  • CORNELL RC, GREENWAY HT, TUCKER SB et al.: Intralesional interferon therapy for basal cell carcinoma. J. Am. Acad. Dermatol. (1990) 23:694-700.
  • EDWARDS L, WHITING D, ROGERS D, LUCK K, SMILES KA: The effect of intralesional interferon gamma on basal cell carcinoma. J. Am. Acad. Dermatol. (1990) 22:496-500.
  • KOOY AJW, TANK B, VUZEVSKI VD, VAN JOOST T, PRENS EP: Expression of interferon-gamma receptors and interferon-gamma-induced up-regulation of intercellular adhesion molecule-1 in basal cell carcinoma; decreased expression of IFN-γR and shedding of ICAM-1 as means to escape immune surveillance. J. Pathol. (1998) 184:169-176.
  • TELFER NR, COLVER GB, BOWERS PW: Guidelines for the management of basal cell carcinoma. British Association of Dermatologists. Br. J. Dermatol. (1999) 141:415-423.
  • VAN DER STRAATEN M, LEE P, WEITZUL S, COCKERELL CJ, TYRING SK: Advances in the treatment of basal cell carcinoma: The promise of pharmacologic therapy. Adv. Dermatol. (2000) 16:299-318.
  • WENNBERG AM: Basal cell carcinoma – new aspects of diagnosis and treatment. Acta Der. Venereol. Suppl. (2000) 209:5-25.
  • BATH-HEXTALL F, BONG F, PERKINS W, WILLIAMS H: Interventions for basal cell carcinoma of the skin: systematic review. Br. Med. J. (2004) 329:705.
  • BURNS CA, BROWN MD: Imiquimod for the treatment of skin cancer. Dermatol. Clin. (2005) 23:151-164.
  • GUPTA AK, CHERMAN AM, TYRING SK: Viral and nonviral uses of imiquimod: a review. J. Cutan. Med. Surg. (2005) (Epub ahead of print).
  • MARKS R, GEBAUER K, SHUMACK S et al.: Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results of a multicenter 6-week dose-response trial. J. Am. Acad. Dermatol. (2001) 44:807-813.
  • SCHÖN MP, WIENRICH BG, DREWNIOK C et al.: Death receptor-independent apoptosis in malignant melanoma induced by the small-molecule immune response modifier imiquimod. J. Invest. Dermatol. (2004) 122:1266-1276.
  • SCHULZE HJ, CRIBIER B, REQUENA L et al.: Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled Phase III study in Europe. Br. J. Dermatol. (2005) 152:939-947.
  • STANLEY MA: Mechanism of action of imiquimod. Papillomavirus Rep. (1999) 10:23-29.
  • UROSEVIC M, DUMMER R: Role of imiquimod in skin cancer treatment. Am. J. Clin. Dermatol. (2004) 5:453-458.
  • STANLEY MA: Imiquimod and the imidazoquinolones: mechanism of action and therapeutic potential. Clin. Exp. Dermatol. (2002) 27:571-577.
  • STOCKFLETH E, MEYER T, BENNINGHOFF B, CHRISTOPHERS E: Successful treatment of actinic keratosis with imiquimod cream 5%: A report of six cases. Br. J. Dermatol. (2001) 144:1050-1053.
  • TYRING S: Imiquimod applied topically: A novel immune response modifier. Skin Therapy Lett. (2001) 6:1-4.
  • BEUTNER KR, GEISSE JK, HELMAN D, FOX TL, GINKEL A, OWENS ML: Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream. J. Am. Acad. Dermatol. (1999) 41:1002-1007.
  • HANNUKSELA-SVAHN A, NORDAL E, CHRISTENSEN OB: Treatment of multiple basal cell carcinomas in the scalp with imiquimod 5% cream. Acta Derm. Venereol. (2000) 80:381-382.
  • KAGY MK, AMONETTE R: The use of imiquimod 5% cream for the treatment of superficial basal cell carcinomas in a basal cell nevus syndrome patient. Dermatol. Surg. (2000) 26:577-578; discussion 578-579.
  • NAVI D, HUNTLEY A: Imiquimod 5% cream and the treatment of cutaneous malignancy. Dermatol. Online J. (2004) 10(1).
  • SIDKY YA, BORDEN EC, WEEKS CE, REITER MJ, HATCHER JF, BRYAN GT: Inhibition of murine tumor growth by an interferon-inducing imidazoquinoline. Cancer Res. (1992) 52:3528-3533.
  • GIBSON SJ, IMBERTSON LM, WAGNER TL: Cellular requirements for cytokine production in response to the immunomodulators imiquimod and S-27609. J. Interferon Cytokine Res. (1995) 15:537-545.
  • MEGYERI K, AU WC, ROSZTOCZY I: Stimulation of interferon and cytokine gene expression by imiquimod and stimulation by Sendai virus utilize similar signal transduction pathways. Mol. Cell. Biol. (1995) 15:2207-2218.
  • MILLER RL, BIRMACHU W, GAL S et al.: Cytokine induction by imiquimod, preclinical results and pharmacology. Chemother. J. (1994) 4:148-149.
  • REITER MJ, TESTERMAN TL, MILLER RL, WEEKS CE, TOMAI MA: Cytokine induction in mice by the immunomodulator imiquimod. J. Leukocyte Biol. (1994) 55:234-240.
  • GIBSON SJ, LINDH JM, RITER TR et al.: Plasmacytoid dendritic cells produce cytokines and mature in response to the TLR7 agonists, imiquimod and resiquimod. Cell. Immunol. (2002) 218:74-86.
  • HEMMI H, KAISHO T, TAKEUCHI O et al.: Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat. Immunol. (2002) 3:196-200.
  • JURK M, HEIL F, VOLLMER J et al.: Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat. Immunol. (2002) 3:499.
  • GORDEN KB, GORSKI KS, GIBSON SJ et al.: Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8. J. Immunol. (2005) 174:1259.
  • WAGNER TL, HORTON VL, CARLSON GL: Induction of cytokines in Cynomolgus monkeys by the immune response modifiers, imiquimod, S-27609 and S-28463. Cytokine (1997) 9:837-845.
  • WEEKS CE, GIBSON SJ: Induction of interferon and other cytokines by imiquimod and its hydroxylated metabolite R-842 in human blood cells in vitro. J. Interferon Cytokine Res. (1994) 14:81-85.
  • UROSEVIC M, DUMMER R, CONRAD C et al.: Disease-independent skin recruitment and activation of plasmacytoid predendritic cells following imiquimod treatment. J. Natl. Cancer Inst. (2005) 97:1143-1153.
  • SULLIVAN TP, DEARAUJO T, VINCEK V, BERMAN B: Evaluation of superficial basal cell carcinomas after treatment with imiquimod 5% cream or vehicle for apoptosis and lymphocyte phenotyping. Dermatol. Surg. (2003) 29:1181-1186.
  • SUZUKI H, WANG B, SHIVJI GM et al.: Imiquimod, a topical immune response modifier, induces migration of Langerhans cells. J. Invest. Dermatol. (2000) 114:135-141.
  • BURNS R, FERBEL B, TOMAI MA, MILLER RL, GASPARI A: The imidazoquinolines, imiquimod and R-848, induce functional, but not phenotypic, maturation of human epidermal Langerhans cells. Clin. Immunol. (2000) 94:13-23.
  • HARRISON CJ, MILLER RL, BERNSTEIN DI: Posttherapy suppression of genital herpes simplex virus (HSV) recurrences and enhancement of HSV-specific T-cell memory by imiquimod in guinea pigs. Antimicrob. Agents Chemother. (1994) 38:2059-2064.
  • BERNSTEIN DI, HARRISON CJ, TEPE ER, SHAHWAN A, MILLER RL: Effect of imiquimod as an adjuvant for immunotherapy of genital HSV in guinea pigs. Vaccine (1995) 13:72-76.
  • ODASHIMA M, BAMIAS G, RIVERA-NIEVES J et al.: Activation of A2A adenosine receptor attenuates intestinal inflammation in animal models of inflammatory bowel disease. Gastroenterol. (2005) 129:26-33.
  • BERMAN B, SULLIVAN TP, DE ARAUJO T, NADJI T: Expression of Fas-receptor on basal cell carcinomas after treatment with imiquimod 5% cream or vehicle. Br. J. Dermatol. (2003) 149(Suppl. 66):59-61.
  • SCHÖN M, BONG AB, DREWNIOK C et al.: Tumor-selective induction of apoptosis and the small-molecule immune response modifier imiquimod. J. Natl. Cancer Inst. (2003) 95:1138-1149.
  • SIDBURY R, NEUSCHLER N, NEUSCHLER E et al.: Topically applied imiquimod inhibits vascular tumor growth in vivo. J. Invest. Dermatol. (2003) 121:1205-1209.
  • SUN XM, MACFARLANE M, ZHUANG J, WOLF BB, GREEN DR, COHEN GM: Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J. Biol. Chem. (1999) 274:5053-5060.
  • DIRSCH VM, STUPPNER H, VOLLMAR AM: Helenalin triggers a CD95 death receptor-independent apoptosis that is not affected by overexpression of Bcl-XL or Bcl-2. Cancer Res. (2001) 61:5817-5823.
  • CRYNS V, YUAN J: Proteases to die for. Genes Dev. (1999) 12:1551-1570.
  • LYSA B, TARTLER U, WOLF R et al.: Gene expression in actinic keratoses: pharmacological modulation by imiquimod. Br. J. Dermatol. (2004) 151:1150-1159.
  • VIDAL D, MATIAS-GUIU X, ALOMAR A: Efficacy of imiquimod for the expression of Bcl-2, Ki67, p53 and basal cell carcinoma apoptosis. Br. J. Dermatol. (2004) 151:656-662.
  • STEINMANN A, FUNK JO, SCHULER G, VON DEN DRIESCH P: Topical imiquimod treatment of a cutaneous melanoma metastasis. J. Am. Acad. Dermatol. (2000) 43:555-556.
  • BONG AB, BONNEKOH B, FRANKE I, SCHÖN MP, ULRICH J, GOLLNICK H: Imiquimod, a novel immune response modifier, in the treatment of cutaneous metastases of malignant melanoma. Dermatology (2002) 205:135-138.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.