# Advancing skin cancer prevention by tackling UV-induced clonogenic mutations

> **NIH NIH R01** · ROSWELL PARK CANCER INSTITUTE CORP · 2021 · $596,193

## Abstract

1 Squamous cell skin cancer (SCC) is the second most common cancer in the US. There are methods available
 2 to prevent SCC but are not appropriately used because we lack methods of evaluating their effectiveness in a
 3 timely manner. Ultraviolet light (UV) from the sun induces genomic damage which is the most important cause
 4 of skin cancer. Early in the process of cancer formation UV causes mutations in cells which result in small
 5 clones, clusters of mutated cells. The early mutations that result in the growth of these clones are called
 6 clonogenic mutations (CM). CMs are early changes during SCC formation, which appear decades before
 7 clinically detectable cancer. Based on previous evidence CMs may signal skin cancer risk and evaluate the
 8 efficacy of preventative treatment strategies and sun protection. CM are in low abundance in the skin which
9 make them challenging to detect. However, recent advances in genomic sequencing technology and
10 computational tools allow accurate identification and quantitation of CMs in the skin. Preliminary data has shown
11 that CMS can be accurately detected and used to evaluate sun damaged skin areas. Many of the CMs found in
12 normal sun exposed skin are also common in SCC. The central hypothesis for this application is that CMs are
13 biomarkers of sun induced skin damaged and that CMs can measure how well strategies for skin cancer
14 prevention and preventative treatment work. In the first set of studies we will refine the previously developed
15 panel of sun induced CMs by identifying the most common CMs in sun exposed versus non-sun exposed skin.
16 Subsequent studies will examine the impact of UV exposure on changes in the CM panel and development of
17 skin cancer. These studies will evaluate patterns of CMs and the risk of developing skin cancer. Next, the
18 refined panel of CMs will be used to examine how well treatments designed to prevent skin cancer in heavily
19 sun damaged skin areas reduce CMs and skin cancer formation. In the final set of studies, CMs will be used to
20 evaluate the efficacy of sun protection strategies, such as sunscreens. Sun protection factor (SPF) is widely
21 used to evaluate sunscreens. However, SPF measures reduction in redness of the skin instead of the actual
22 DNA damage. Genomic DNA damage contributes to skin cancer, not “redness” in the skin. Genomic damage
23 can be caused by long term sun damage that does not cause a sunburn. In the final set of studies, CMs are used
24 to evaluate the effectiveness of sunscreens to protect against genomic damage and skin cancer. These studies
25 will change how we evaluate a patient’s risk of developing skin cancer and how we determine the effect of skin
26 cancer prevention. These studies have the potential to shift the focus from treating cancer to preventing the
27 occurrence of skin cancer. This would result in an improvement in cancer care outcomes, improve treatment
28 strategies and ultimately improve th...

## Key facts

- **NIH application ID:** 10097574
- **Project number:** 1R01CA255242-01
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** GYORGY PARAGH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $596,193
- **Award type:** 1
- **Project period:** 2021-02-03 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10097574

## Citation

> US National Institutes of Health, RePORTER application 10097574, Advancing skin cancer prevention by tackling UV-induced clonogenic mutations (1R01CA255242-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10097574. Licensed CC0.

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