Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream

Beutner, Karl R.; Geisse, John K.; Helman, Donita; Fox, Terrance L.; Ginkeld, Angela; Owens, Mary

doi:10.1016/s0190-9622(99)70261-6

Cited by 348 publications

(296 citation statements)

References 22 publications

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“…This newly discovered IMQ-independent activity of Aldara might explain the therapeutic efficacy of the placebo, which was observed in most clinical trials that included a placebo-control group 1,2,48 . The fact that the clinical response of Aldara-treated patients was always greater than that of the placebo-treated patients suggests that the IMQ-dependent and -independent pathway must act in concert for optimal efficacy.…”

Section: Discussionmentioning

confidence: 84%

Aldara activates TLR7-independent immune defence

et al. 2013

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Aldara is a cream used for topical treatment of non-melanoma skin cancer, and is thought to act through stimulation of anti-tumour immunity. The active ingredient, imiquimod, has been shown to stimulate toll-like receptor 7. Aldara also induces psoriasis-like lesions when applied to naive murine skin, and as such is used as a mouse model for psoriasis. Here we find that in naive murine skin, Aldara induces inflammation largely independently of toll-like receptor 7. Surprisingly, inflammasome activation, keratinocyte death and interleukin 1 release also occur in response to the vehicle cream in the absence of imiquimod. We show that isostearic acid, a major component of the vehicle, promotes inflammasome activation in cultured keratinocytes, and so may contribute to the observed effects of Aldara on murine skin. Aldara therefore stimulates at least two immune pathways independently, and both imiquimod and vehicle are required for a full inflammatory response. Although it remains to be tested, it is possible that imiquimod-independent effects also contribute to the therapeutic efficacy of Aldara.

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Section: Discussionmentioning

confidence: 84%

Aldara activates TLR7-independent immune defence

et al. 2013

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“…Various regimens of imiquimod have been used in practice, including application twice daily, once daily, and every other day; applications have been performed with and without occlusion for treatment courses ranging from 6 to 16 weeks. 45,[64][65][66][67][68][69][70][71][72][73] Overall, rates of 3-to 12-month clinical and histologic cure have been reported to range from 60% to 80% in well-designed RCTs, with the highest rates reported for shorter follow-up and clinical J AM ACAD DERMATOL VOLUME jj, NUMBER j cure. Moderate-to-severe local treatment-associated adverse events include skin redness, swelling, erosions, crusts, vesicles, itching, and, occasionally, tingling sensations.…”

Section: Topical Therapiesmentioning

confidence: 99%

Guidelines of care for the management of basal cell carcinoma

Baum¹,

Bordeaux²,

Brown³

et al. 2018

Journal of the American Academy of Dermatology

315

219

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Basal cell carcinoma (BCC) is the most common form of human cancer, with a continually increasing annual incidence in the United States. When diagnosed early, the majority of BCCs are readily treated with office-based therapy, which is highly curative. In these evidence-based guidelines of care, we provide recommendations for the management of patients with BCC, as well as an in-depth review of the best available literature in support of these recommendations. We discuss biopsy techniques for a clinically suspicious lesion and offer recommendations for the histopathologic interpretation of BCC. In the absence of a formal staging system, the best available stratification based on risk for recurrence is reviewed. With regard to treatment, we provide recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy. Finally, we review the available literature and provide recommendations on prevention and the most appropriate follow-up for patients in whom BCC has been diagnosed. ( J Am Acad Dermatol

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“…Imiquimod, a novel imidazoquinoline immune response modiWer, has been approved for topical treatment of anogenital warts and has shown eYcacy in superWcial basal cell carcinomas and actinic keratoses [1,24]. When applied topically, imiquimod induces T lymphocytic inWltrates via its binding to toll-like receptor 7 (TLR7) and stimulation of various cytokines.…”

Section: Introductionmentioning

confidence: 99%

Imiquimod induces apoptosis of human melanocytes

et al. 2009

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Development of vitiligo-like hypopigmentary lesions associated with topical imiquimod has been reported. We hypothesized that mode of action of imiquimod in melanocytes may include triggering of apoptosis resulted in loss of cells, which may be a possible mechanism of imiquimod-induced hypopigmentary lesions. Therefore, we investigated whether imiquimod induces apoptosis of human melanocytes and also whether it modulates expression of apoptosis-related molecules in human melanocytes. Imiquimod treatment induced apoptosis of melanocytes, which was observed by TUNEL assay and Hoechst 33258 staining. Imiquimod-induced apoptosis was further shown by measuring mitochondrial membrane potential in melanocytes. The apoptotic activity of imiquimod was associated with caspase-3, Bcl-2 and mitogenactivated protein kinase expression in melanocytes. These results indicated that imiquimod induces apoptosis of melanocytes. These Wndings may provide a clue to understand pathogenesis of imiquimod-induced vitiligo-like hypopigmentary lesions.

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Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream

Cited by 348 publications

References 22 publications

Aldara activates TLR7-independent immune defence

Aldara activates TLR7-independent immune defence

Guidelines of care for the management of basal cell carcinoma

Imiquimod induces apoptosis of human melanocytes

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