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Topical kinase inhibitors induce regression of cutaneous squamous cell carcinoma
Author(s) -
Yang Xiaoping,
Daifallah Aliaa E. M.,
Shankar Shiela,
Beer Jacob,
Marshall Christine,
Dentchev Tzvete,
Seykora Francesca,
D'Armas Sebastian,
Hahn Jaeyi,
Lee Vivian,
Sabry Hanan H.,
Farag Assem M.,
Seykora John T.
Publication year - 2019
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13902
Subject(s) - dasatinib , medicine , cancer research , keratinocyte , skin cancer , carcinoma , cancer , kinase , erythema , immunology , pathology , biology , cell culture , myeloid leukemia , microbiology and biotechnology , imatinib , genetics
Abstract Actinic keratoses ( AK s) and squamous cell carcinoma in situ ( SCCIS ) are precursor lesions for cutaneous squamous cell carcinoma ( cSCC ), the second most common form of cancer. Current topical therapies for AK s and SCCIS promote skin inflammation to eradicate lesions and do not directly target the biological mechanisms driving growth. We hypothesized that topical small molecule inhibitors targeting kinases promoting keratinocyte growth in AK s and SCCIS could induce regression of these lesions with less inflammation. To test this hypothesis, we determined the efficacy of topical dasatinib, 5‐fluorouracil and BEZ ‐235 in inducing regression of cSCC s in the K14‐Fyn Y528 transgenic mouse model. Topical dasatinib induced regression of cSCC with less inflammation, no ulceration and no mortality compared to 5‐fluorouracil. Topical BEZ ‐235 induced cSCC regression similar to dasatinib without erythema or ulceration. These data indicate that topical small molecule kinase inhibitors targeting drivers of AK / SCCIS / cSCC growth represent a promising therapeutic approach to treat these common skin lesions.