# Wounding Therapy and Photocarcinogenesis

> **NIH NIH R01** · WRIGHT STATE UNIVERSITY · 2022 · $472,255

## Abstract

ABSTRACT
Non-melanoma skin cancer (NMSC) is a disease primarily afflicting geriatric patients as evidenced by the fact
that 80% of all non-melanoma skin cancers are diagnosed in patients over the age of 60 years. As such,
geriatric skin responds to cancer-inducing ultraviolet B (UVB) irradiation in a manner that allows the
establishment of tumor cells. While the correlation between aged epidermis and skin cancer is obvious, the
mechanism responsible for this relationship remains obscure. Recent in vitro evidence as well as
epidemiological data suggests one possible mechanism may involve alterations in the insulin-like growth
factor-1 receptor (IGF-1R) signaling network. Using normal human keratinocytes grown in vitro, activated IGF-
1Rs protect keratinocytes from UVB-induced apoptosis; however, while UVB-irradiated keratinocytes with
activated IGF-1Rs survive, they are incapable of further cellular replication, in fact they are senescent. The
critically important observation was that in the absence of IGF-1R activation, keratinocytes are more sensitive
to UVB-induced apoptosis, but the keratinocytes that do survive retain the capacity to proliferate. In the skin,
keratinocytes express the IGF-1R but they do not synthesize IGF-1. Dermal fibroblasts support the proliferation
of keratinocytes in the epidermis by secreting IGF-1. Interestingly, as dermal fibroblasts age, their capacity to
produce IGF-1 is severely diminished; therefore, in aged skin keratinocytes are provided with a reduced supply
of IGF-1 and a concomitant reduction in IGF-1R activation. We have demonstrated that geriatric skin responds
to UVB irradiation in a manner that could lead to initiated carcinogenic keratinocytes. This inappropriate UVB
response can be corrected by treatment with exogenous IGF-1. Furthermore, we have shown that treatment of
geriatric skin with non-ablative dermal rejuvenation therapies can re-establish youthful IGF-1 levels and
subsequently reinstate the appropriate UVB response on geriatric skin. Moreover, we have demonstrated this
protection to acute UVB exposure is durable for up to two years. In this proposal, we will continue and expand
our ongoing clinical trials on the prophylactic effect of non-ablative wounding therapies to both treat and
prevent UVB-induced skin cancer. In particular, we will recruit post-menopausal females for these studies as
this is an underserved population for skin cancer studies. A novel non-invasive mesoscopic imaging platform
will be used to monitor actinic neoplasia progression. In addition, we will examine the mechanisms responsible
for the ability of non-ablative wounding therapies to increase fibroblast-associated IGF-1 expression. These
studies will have a major impact on the treatment of NMSC by establishing a novel anti-carcinogenic role for
dermal wounding. Furthermore, the data from these studies will confirm a new paradigm defining the
mechanism of age-associated skin cancer. Outcomes for these studies include no...

## Key facts

- **NIH application ID:** 10520135
- **Project number:** 2R01AG048946-07A1
- **Recipient organization:** WRIGHT STATE UNIVERSITY
- **Principal Investigator:** DAN F SPANDAU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $472,255
- **Award type:** 2
- **Project period:** 2014-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520135

## Citation

> US National Institutes of Health, RePORTER application 10520135, Wounding Therapy and Photocarcinogenesis (2R01AG048946-07A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10520135. Licensed CC0.

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