TY - JOUR
T1 - Pathobiology of actinic keratosis
T2 - Ultraviolet-dependent keratinocyte proliferation
AU - Berman, Brian
AU - Cockerell, Clay J.
AU - Zografos, Panagiotis
N1 - Funding Information:
Publication of this article was supported by a grant from LEO Pharma Inc. , Parsippany, NJ.
PY - 2013/1
Y1 - 2013/1
N2 - Actinic keratoses are proliferations of transformed neoplastic keratinocytes in the epidermis that are the result of cumulative ultraviolet (UV) radiation from sun exposure. They are commonly found on sites of sun-exposed skin such as the face, balding scalp, and back of the hand. Although UV exposure does exert certain beneficial effects on the skin, excessive exposure to UV radiation induces multiple cascades of molecular signaling events at the cellular level that produce inflammation, immunosuppression, failure of apoptosis, and aberrant differentiation. Cumulatively, these actions result in mutagenesis and, ultimately, carcinogenesis. This article provides a brief overview of the key mediators that are implicated in the pathobiology of actinic keratosis. Three evolutionary possibilities exist for these keratoses in the absence of treatment: (1) spontaneous remission, which can be common; (2) remaining stable, without further progression; or (3) transformation to invasive squamous cell carcinoma, which may metastasize. Because the effects of UV radiation on the skin are complex, it is not yet fully clear how all of the mediators of actinic keratosis progression are interrelated. Nonetheless, some represent potential therapeutic targets, because it is clear that directing therapy to the effects of UV radiation at a number of different levels could interrupt and possibly reverse the mechanisms leading to malignant transformation.
AB - Actinic keratoses are proliferations of transformed neoplastic keratinocytes in the epidermis that are the result of cumulative ultraviolet (UV) radiation from sun exposure. They are commonly found on sites of sun-exposed skin such as the face, balding scalp, and back of the hand. Although UV exposure does exert certain beneficial effects on the skin, excessive exposure to UV radiation induces multiple cascades of molecular signaling events at the cellular level that produce inflammation, immunosuppression, failure of apoptosis, and aberrant differentiation. Cumulatively, these actions result in mutagenesis and, ultimately, carcinogenesis. This article provides a brief overview of the key mediators that are implicated in the pathobiology of actinic keratosis. Three evolutionary possibilities exist for these keratoses in the absence of treatment: (1) spontaneous remission, which can be common; (2) remaining stable, without further progression; or (3) transformation to invasive squamous cell carcinoma, which may metastasize. Because the effects of UV radiation on the skin are complex, it is not yet fully clear how all of the mediators of actinic keratosis progression are interrelated. Nonetheless, some represent potential therapeutic targets, because it is clear that directing therapy to the effects of UV radiation at a number of different levels could interrupt and possibly reverse the mechanisms leading to malignant transformation.
KW - actinic keratosis
KW - apoptosis
KW - immunosuppression
KW - keratinocyte carcinogenesis
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=84870895234&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870895234&partnerID=8YFLogxK
U2 - 10.1016/j.jaad.2012.09.053
DO - 10.1016/j.jaad.2012.09.053
M3 - Article
C2 - 23228301
AN - SCOPUS:84870895234
SN - 0190-9622
VL - 68
SP - S10-S19
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 1 SUPPL.1
ER -