R01CA255242

Advancing Skin Cancer Prevention by Tackling UV-Induced Clonogenic Mutations

Squamous cell skin cancer (SCC) is the second most common cancer in the US. There are methods available to prevent SCC but are not appropriately used because we lack methods of evaluating their effectiveness in a timely manner.

Ultraviolet light (UV) from the sun induces genomic damage which is the most important cause of skin cancer. Early in the process of cancer formation, UV causes mutations in cells which result in small clones, clusters of mutated cells. The early mutations that result in the growth of these clones are called clonogenic mutations (CM). CMs are early changes during SCC formation, which appear decades before clinically detectable cancer. Based on previous evidence, CMs may signal skin cancer risk and evaluate the efficacy of preventative treatment strategies and sun protection.

CMs are in low abundance in the skin which make them challenging to detect. However, recent advances in genomic sequencing technology and computational tools allow accurate identification and quantitation of CMs in the skin. Preliminary data has shown that CMs can be accurately detected and used to evaluate sun damaged skin areas. Many of the CMs found in normal sun exposed skin are also common in SCC. The central hypothesis for this application is that CMs are biomarkers of sun-induced skin damage and that CMs can measure how well strategies for skin cancer prevention and preventative treatment work.

In the first set of studies, we will refine the previously developed panel of sun-induced CMs by identifying the most common CMs in sun exposed versus non-sun exposed skin. Subsequent studies will examine the impact of UV exposure on changes in the CM panel and development of skin cancer. These studies will evaluate patterns of CMs and the risk of developing skin cancer.

Next, the refined panel of CMs will be used to examine how well treatments designed to prevent skin cancer in heavily sun damaged skin areas reduce CMs and skin cancer formation. In the final set of studies, CMs will be used to evaluate the efficacy of sun protection strategies, such as sunscreens. Sun protection factor (SPF) is widely used to evaluate sunscreens. However, SPF measures reduction in redness of the skin instead of the actual DNA damage. Genomic DNA damage contributes to skin cancer, not "redness" in the skin. Genomic damage can be caused by long term sun damage that does not cause a sunburn. In the final set of studies, CMs are used to evaluate the effectiveness of sunscreens to protect against genomic damage and skin cancer. These studies will change how we evaluate a patient's risk of developing skin cancer and how we determine the effect of skin cancer prevention.

These studies have the potential to shift the focus from treating cancer to preventing the occurrence of skin cancer. This would result in an improvement in cancer care outcomes, improve treatment strategies, and ultimately improve the life of individuals with a history of sun damage and pre-cancerous lesions. This work focuses on skin cancer but as CMs play a crucial first step in cancer growth in most human cancers, our findings and the framework of this study will have implications for the wider field of preventative oncology.

Health Research

TO IMPROVE SCREENING AND EARLY DETECTION STRATEGIES AND TO DEVELOP ACCURATE DIAGNOSTIC TECHNIQUES AND METHODS FOR PREDICTING THE COURSE OF DISEASE IN CANCER PATIENTS. SCREENING AND EARLY DETECTION RESEARCH INCLUDES DEVELOPMENT OF STRATEGIES TO DECREASE CANCER MORTALITY BY FINDING TUMORS EARLY WHEN THEY ARE MORE AMENABLE TO TREATMENT. DIAGNOSIS RESEARCH FOCUSES ON METHODS TO DETERMINE THE PRESENCE OF A SPECIFIC TYPE OF CANCER, TO PREDICT ITS COURSE AND RESPONSE TO THERAPY, BOTH A PARTICULAR THERAPY OR A CLASS OF AGENTS, AND TO MONITOR THE EFFECT OF THE THERAPY AND THE APPEARANCE OF DISEASE RECURRENCE. THESE METHODS INCLUDE DIAGNOSTIC IMAGING AND DIRECT ANALYSES OF SPECIMENS FROM TUMOR OR OTHER TISSUES. SUPPORT IS ALSO PROVIDED FOR ESTABLISHING AND MAINTAINING RESOURCES OF HUMAN TISSUE TO FACILITATE RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.394 - Cancer Detection and Diagnosis Research

National Cancer Institute (NCI) [HHS - NIH]

Buffalo, New York 14263 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the End Date has been extended from 01/30/26 to 01/31/26 and the total obligations have increased 552% from $493,265 to $3,218,488.