A Randomized, Double-blind, Vehicle-Controlled Study to Assess 5% Imiquimod Cream for the Treatment of Multiple Actinic Keratoses

Stockfleth, Eggert; Meyer, Thomas; Benninghoff, Bernd; Salasche, Stuart J.; L, Papadopoulos; Ulrich, Claas; Christophers, Enno

doi:10.1001/archderm.138.11.1498

Cited by 186 publications

(128 citation statements)

References 17 publications

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…They found that imiquimod treatment was associated with partial or total reversal of the aberrant expression of some genes in AK, thereby demonstrating the ability of imiquimod to prevent the development of cancer. This statement was confirmed by others, showing that imiquimod treatment results in clearing of AK lesions [113][114][115][116].…”

Section: Current Use Of Tlr7/8 Ligands In Cancer Treatment and Cancersupporting

confidence: 68%

The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy

et al. 2008

View full text Add to dashboard Cite

After completing this course, the reader should be able to:1. Describe the subtypes of Toll-like receptor 7 and 8 agonists and their effect on the different components of the antitumor immune response.2. Argue why they are used as stand-alone immunotherapeutic agents.3. Evaluate their potential to improve current approaches of active and passive immunotherapy.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACT

show abstract

Section: Current Use Of Tlr7/8 Ligands In Cancer Treatment and Cancersupporting

confidence: 68%

The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy

et al. 2008

View full text Add to dashboard Cite

show abstract

“…In addition, several controlled clinical trials as well as many smaller series of cases and case reports have demonstrated that imiquimod is also effective against a variety of primary skin cancers as well as cutaneous metastases of some malignancies. Cutaneous tumors that have responded well to topical treatment with imiquimod include basal cell carcinomas (Sterry et al, 2002;BathHextall et al, 2004;Geisse et al, 2004;Gollnick et al, 2005;Schulze et al, 2005), keratoacanthomas (Dendorfer et al, 2003;Peris et al, 2003), actinic keratoses (Stockfleth et al, 2001(Stockfleth et al, , 2002Lebwohl et al, 2004;Szeimies et al, 2004;Korman et al, 2005) and Bowen's disease (the latter two entities represent epidermal carcinoma in situ) (Patel et al, 2006;Peris et al, 2006), cutaneous metastases of melanoma (Steinmann et al, 2000;Bong et al, 2002;Ugurel et al, 2002;Wolf et al, 2003;Zeitouni et al, 2005), some cases of primary melanoma in situ (Fleming et al, 2004;Kamin et al, 2005;Ray et al, 2005;Wolf et al, 2005;Lonsdale-Eccles et al, 2006) and cutaneous T-cell lymphomas (Suchin et al, 2002;Dummer et al, 2003b;Chong et al, 2004;Deeths et al, 2005). Clinical responses of cutaneous neoplasias to topical treatment with imiquimod have also been observed in difficult-to-treat patient populations, such as organ transplant patients under immunosuppressive therapy (Smith et al, 2001;Prinz et al, 2004;Brown et al, 2005) or Xeroderma pigmentosum patients suffering from rapid development of multiple UV-induced cutaneous malignancies …”

Section: Antitumoral Efficacy Of Tlr7/8 Agonists In Clinical Trialsmentioning

confidence: 99%

TLR7 and TLR8 as targets in cancer therapy

2008

View full text Add to dashboard Cite

Small-molecule agonists at Toll-like receptor 7 (TLR7) and TLR8 have sparked a vivid interest in cancer research owing to their profound antitumoral activity. The lead compound of the imidazoquinoline family, imiquimod, is marketed as a topical formulation. It is efficacious against many primary skin tumors and cutaneous metastases. Using different imidazoquinoline species, distinct functions of TLR7 and TLR8 have been discovered. The predominant antitumoral mode of action of these agents is TLR7/ 8-mediated activation of the central transcription factor nuclear factor-jB, which leads to induction of proinflammatory cytokines and other mediators. Cutaneous dendritic cells are the primary responsive cell type and initiate a strong Th1-weighted antitumoral cellular immune response. Recent research has shown that dendritic cells themselves acquire direct antitumoral activity upon stimulation by imiquimod. In addition, there are a number of secondary effects on the molecular and cellular level that can be explained through the activation of TLR7/8. The proinflammatory activity of imiquimod, but not resiquimod, appears to be augmented by suppression of a regulatory mechanism, which normally limits inflammatory responses. This is achieved independently of TLR7/8 through interference with adenosine receptor signaling pathways. Finally, at higher concentrations imiquimod exerts Bcl-2-and caspase-dependent proapoptotic activity against tumor cells.

show abstract

“…It is used for the treatment of genital warts, caused by human papilloma virus infection, and for the treatment of malignant tumors of the skin. Cutaneous tumors that have responded well to topical treatment with imiquimod include basal cell carcinomas (Sterry et al, 2002;Geisse et al, 2004;Schulze et al, 2005), actinic keratosis (Stockfleth et al, 2002;Szeimies et al, 2004;Korman et al, 2005;Hadley et al, 2006), keratoacanthomas (Dendorfer et al, 2003), and cutaneous metastases of melanoma (Bong et al, 2002;Ugurel et al, 2002). Another imidazoquinoline, resiquimod, has also been evaluated in a clinical Phase II study on actinic keratosis, with positive results (Szeimies et al, 2008).…”

Section: Introductionmentioning

confidence: 99%