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Ingenol mebutate: a succinct review of a succinct therapy.

ABSTRACT:

Background

Ingenol mebutate is a newly approved topical field therapy for actinic keratosis (AK). It has a dual mechanism of action comprising of a rapid induction of necrosis that specifically targets dysplastic cells, as well as neutrophil-mediated immunostimulatory effects. Such a dual mechanism allows for this agent to clear AK lesions in as little as two to three daily applications, thus providing for improved treatment outcomes and patient satisfaction.

Review

Given that this is a new dermatologic therapy, this review summarizes the key literature surrounding this agent. This review covers the indications for use, mechanisms of action, method of administration, efficacy and safety profile and important drug interactions of ingenol mebutate.

Conclusions

Ingenol mebutate should be considered a highly relevant field therapy for AK and the prevention of progression to squamous cell carcinoma.

SUBMITTER: Alchin DR

PROVIDER: S-EPMC4257954 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Actinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma if left untreated. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood. In this study, we evaluated the gene expression profiles of actinic keratosis lesions before and after treatment with ingenol mebutate using microarray technology. Actinic keratoses on face/scalp of 15 immunocompetent patients were identified and evaluated after treatment with topical ingenol mebutate gel 0.015%, applied once daily for 3 consecutive days. Diagnostic and clearance of lesions was determined by clinical, dermoscopic, and reflectance confocal microscopy criteria. Lesional and non-lesional skin biopsies were subjected to gene expression analysis profiled by Affymetrix microarray. Differentially expressed genes were identified, and enrichment analyses were performed using STRING database. At 8 weeks post-treatment, 60% of patients responded to ingenol mebutate therapy, achieving complete clearance in 40% of cases. A total of 128 differentially expressed genes were identified following treatment, and downregulated genes (114 of 128) revealed changes in pathways important to epidermal development, keratinocyte differentiation and cornification. In responder patients, 388 downregulated genes (of 450 differentially expressed genes) were also involved in development/differentiation of the epidermis, and immune system-related pathways, such as cytokine and interleukin signaling. Cluster analysis revealed two relevant clusters showing upregulated profile patterns in pre-treatment actinic keratoses of responders, as compared to non-responders. Again, differentially expressed genes were mainly associated with cornification, keratinization and keratinocyte differentiation. Overall, the present study provides insight into the gene expression profile of actinic keratoses after treatment with ingenol mebutate, as well as identification of genetic signatures that could predict treatment response.