title: Ingenol mebutate field-directed treatment of UVB-damaged skin reduces lesion formation and removes mutant p53 patches.
abstract: Skin cancer is the most prevalent cancer worldwide and is primarily caused by chronic UV exposure. Here, we describe the topical field-directed treatment of SKH1/hr mice with UVB-damaged skin with ingenol mebutate, a new topical drug shown to be effective for the treatment of actinic keratosis (AK). Application of 0.05% ingenol mebutate gel to photo-damaged skin resulted in a ≈70% reduction in the number of skin lesions that subsequently emerged compared with placebo treatment. Ingenol mebutate treatment also reduced the number of mutant p53 keratinocyte patches by ≈70%. The treatment resulted in epidermal cell death, acute inflammation, recruitment of neutrophils, hemorrhage, and eschar formation, all of which resolved over several weeks. Ingenol mebutate field-directed treatment might thus find utility in the removal of subclinical precancerous cells from UV-damaged skin. Field-directed treatment may be particularly suitable for patients who have AKs surrounded by UV-damaged skin.
authors.affiliation: Department of Immunology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Sarah-Jane
authors.initials: SJ
authors.lastname: Cozzi
authors.forename: Steven M
authors.initials: SM
authors.lastname: Ogbourne
authors.forename: Cini
authors.initials: C
authors.lastname: James
authors.forename: Heggert G
authors.initials: HG
authors.lastname: Rebel
authors.forename: Frank R
authors.initials: FR
authors.lastname: de Gruijl
authors.forename: Blake
authors.initials: B
authors.lastname: Ferguson
authors.forename: Joy
authors.initials: J
authors.lastname: Gardner
authors.forename: Thuy T
authors.initials: TT
authors.lastname: Lee
authors.forename: Thibaut
authors.initials: T
authors.lastname: Larcher
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D055623:Keratosis, Actinic / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D009154:Mutation / Q000235:genetics; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000517:prevention & control; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C486592:3-ingenyl angelate; D000970:Antineoplastic Agents; D004224:Diterpenes; D016159:Tumor Suppressor Protein p53