Fibroblast Senescence and Squamous Cell Carcinoma: How Wounding Therapies Could Be Protective

Abstract

Background Squamous cell carcinoma (SCC), which has one of the highest incidences of all cancers in the United States, is an age-dependent disease as the majority of these cancers are diagnosed in people over 70 years of age. Recent findings have led to a new hypothesis on the pathogenesis of SCC. Objectives To evaluate the potential of preventive therapies to reduce the incidence of SCC in at-risk geriatric patients. Materials and Methods Survey of current literature on wounding therapies to prevent SCCs. Results This new hypothesis of SCC photocarcinogenesis states that senescent fibroblasts accumulate in geriatric dermis resulting in a reduction in dermal insulin-like growth factor-1 (IGF-1) expression. This lack of IGF-1 expression sensitizes epidermal keratinocytes to fail to suppress UVB-induced mutations leading to increased proclivity to photocarcinogenesis. Recent evidence suggests that dermal wounding therapies, specifically dermabrasion and fractionated laser resurfacing, can decrease the proportion of senescent dermal fibroblasts, increase dermal IGF-1 expression, and correct the inappropriate UVB response found in geriatric skin, thus protecting geriatric keratinocytes from UVB-induced SCC initiation. Conclusions In this review, we will discuss the translation of pioneering basic science results implicating commonly used dermal fibroblast rejuvenation procedures as preventative treatments for SCC.

Important Implications and New Uses of Ablative Lasers in Dermatology

“…8 The IGF-1 system seems to be critical in regulating keratinocyte responses to UVB. It is possible that the laser treatment could be removing UV-initiated cells.…”

Skin resurfacing procedures: new and emerging options

“…Prevention of these skin cancers before they develop is important not only due to these increasing skin cancer numbers, but also because of the large financial cost of treatment and potential disfiguration associated with these types of neoplasia. Current treatments such as cryotherapy, electrosurgery, curettage, PDT, and topical medicines like 5-FU or imiquimod work through physical, chemical or immune-mediated destruction of established precancerous or low-grade lesions 75. These treatments focus only on the precancerous and tumor cells and do not address the underlying processes that cause aged skin to be more susceptible to neoplasia.…”

How Wounding via Lasers Has Potential Photocarcinogenic Preventative Effects via Dermal Remodeling

“…These DNA alterations are not sufficient to cause the keratinocytes death but rather allow them to silently persist in epidermis for decades where they will progressively accumulate novel and certainly deleterious mutations. When the number of these DNA mutations in essential regulatory genes reaches still not defined threshold, abnormal keratinocyte divisions will ensue, initiating the tumor growth and making the cancer clinically apparent (20). However, this traditional approach of accumulation of chromosomal impairments has being non-selectively applied to many neoplastic processes in oncology.…”

“…Keratinocytes with slightly damaged DNA are able to completely repair their genome and survive independently of the IGF-1R activity. Similarly, cells with substantially damaged DNA cannot be rescued by preserved IGF-1R activity and are entirely removed from skin by apoptosis (20). …”

“…It has been shown that if treat AK by these modalities early enough that the progression to SCC is highly unlikely. Still some patients do develop SCC recurrences within 2–5 year period advocating prolonged clinical surveillance of pre-cancerous lesions and consequently increasing financial cost to our healthcare system (20,34). …”