Abstract
The occurrence of non-melanoma skin cancer (NMSC) is closely linked with advanced age and ultraviolet-B (UVB) exposure. More specifically, the development of NMSC is linked to diminished insulin-like growth factor-1 (IGF-1) signaling from senescent dermal fibroblasts in geriatric skin. Consequently, keratinocyte IGF-1 receptor (IGF-1R) remains inactive, resulting in failure to induce appropriate protective responses including DNA repair and cell cycle checkpoint signaling. This allows UVB-induced DNA damage to proliferate unchecked, which increases the likelihood of malignant transformation. NMSC is estimated to occur in 3.3 million individuals annually. The rising incidence results in increased morbidity and significant healthcare costs, which necessitate identification of effective treatment modalities. In this review, we highlight the pathogenesis of NMSC and discuss the potential of novel preventative therapies. In particular, wounding therapies such as dermabrasion, microneedling, chemical peeling, and fractionated laser resurfacing have been shown to restore IGF-1/IGF-1R signaling in geriatric skin and suppress the propagation of UVB-damaged keratinocytes. This wounding response effectively rejuvenates geriatric skin and decreases the incidence of age-associated NMSC.
Highlights
Skin is the largest and most-exposed organ of the body
Though the translesion synthesis (TLS) polymerase pol eta can accurately replicate UV photoproducts, we found that its induction by UVB exposure is partially abrogated by the loss of insulin-like growth factor-1 (IGF-1) signaling in keratinocytes and human skin explants [68]
Our group is currently exploring trichloroacetic acid (TCA) peels in this regard, and our preliminary studies indicate that a 10% TCA peel on geriatric skin upregulates IGF-1 mRNA levels approximately two-fold at 90 days
Summary
Skin is the largest and most-exposed organ of the body. It functions as a barrier against environmental pressures, such as ultraviolet (UV) radiation [1]. Geriatric skin exhibits suppressed IGF-1 signaling due to an increased cellular senescence profile of fibroblasts [11, 12, 19] This has severe consequences in the protective response to UVB radiation whereby keratinocytes may have different destinies depending on the extent of DNA damage and state of IGF-1/ IGF-1R signaling [11, 12, 19]. Novel treatments aimed for geriatric patients both predisposed and exposed to NMSC have been developed One such modality is wounding therapy, which attempts to reverse the geriatric fibroblast senescence phenotype by inducing a “wounding response” [19,20,21,22,23]. The therapies of dermabrasion, microneedling, chemical peeling, and fractionated laser resurfacing will be discussed in the context of prevention of photocarcinogenesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
