Topical medications can regress giant congenital nevi and prevent skin cancer

About one in 20,000 children are born with what is called a giant congenital nevus – a huge, pigmented mole that can cover much of the face and body. Due to the appearance of the mole and its risk of later turning into skin cancer, many patients decide to have their children undergo major surgery to remove the entire lesion, which can cause scarring. important and permanent. Researchers led by researchers at Massachusetts General Hospital (MGH) recently created several preclinical models of this condition and used them to show that several drugs can be applied to the skin to regress the lesions, and that a topical drug protects also against skin cancer. Their findings are published in the journal Cell.

The objectives of our study were to develop a series of animal models designed to elucidate the main biological characteristics of these lesions and to test non-surgical drug treatments on the skin, aimed at shrinking the cells of the nevus, thus removing the need for treatments. surgical.

David E. Fisher, MD, PhD, lead author, Director of the MGH Cancer Center Melanoma Program and Director of the MGH Skin Biology Research Center

The models included mice engineered to express a gene called NRAS which contains a mutation known to cause most congenital giant moles in humans, as well as mice with transplanted skin grafts containing human congenital giant moles. Fisher and his colleagues used these models to analyze the different phases of these nevi to better understand how they form and grow. Additionally, when scientists used the models to test topical applications of single or combination drugs that block signaling pathways known to be activated by NRAS mutations, they found that some of the treatments resulted in significant nevus regressions. Additionally, a drug that stimulates a type of inflammatory reaction when applied topically to the skin caused nevi to shrink completely after three treatments. The therapy also offered complete prevention against the formation of skin cancers in the mice.

“We hope these findings will pave the way for further improvements aimed at directly testing these skin treatments on patients with congenital giant nevi,” says Fisher. “This work will include additional safety studies, further potential improvements in efficacy, and further analysis of the underlying mechanisms. The overall goals are to prevent melanoma in these patients and also to avoid the problems disfigurement of these lesions.”


Massachusetts General Hospital

Journal reference:

Choi, YS, et al. (2022) Topical therapy for regression and prevention of congenital giant nevi melanoma. Cell.

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