Institute scientists develop technologies to reduce the severity of skin cancers

In a recent paper in Nature Scientific Reports, Drs. McCullough and Lloyd report findings on prevention of skin cancer with DNA repair enzymes. These enzymes, normally produced in yeast, were enclosed into a lotion and applied like a sunscreen onto mouse skin, and tested for their ability to prevent non-melanoma skin cancers (NMSCs). Their data showed significant reductions in tumor burden in mice receiving the lotion containing the DNA repair enzyme relative to control lotion. These data suggest that efficient delivery of additional DNA repair enzymes to skin can prevent or delay the onset of NMSCs.

NMSCs, including basal cell carcinoma and squamous cell carcinoma are the most prevalent types of human cancers, affecting over five million people in the United States each year, and costing billions of dollars for health care and loss of work. In addition to high rates of disease in the general population, organ transplant patients have a greater than 50-fold increase in the incidence of NMSC, with increased risk of metastasis. Current methods for treatment of NMSC, including surgical resection of the tumor, are associated with considerable pain and morbidity. Given these exceptionally high incidence rates, strategies to prevent skin cancer have predominantly focused on recommendations for sun avoidance, restricted access of youth to tanning beds, the use of broad spectrum UVA and UVB sunscreens, and application of topical anti-oxidants. However, these recommendations have not sufficiently diminished the prevalence of NMSC, and development of novel methods to reduce or prevent NMSCs would not only alleviate suffering, but also substantially reduce health care costs.

Exposure to UV irradiation in sunlight causes NMSC by inducing several types of DNA damage that if replicated, lead to mutations and cancer. Humans have only one mechanism for repairing the most prominent forms of DNA damage and it is very inefficient. Following even a mild sunburn, the majority of DNA damage is still unrepaired days after the sunlight exposure. In contrast to humans, some organisms can utilize a different DNA repair pathway, with a specific critical enzyme to start the repair process. Drs. McCullough and Lloyd have designed and implemented a strategy to activate this second DNA repair pathway to rapidly accelerate the repair of sunlight-induced DNA damage and reduce the frequency and size of NMSCs.

Learn more about this work by reading the Nature Scientific Reports and visit the Lloyd & McCullough Lab Page.

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