New treatment can help regress congenital giant nevi.
Skin cancer is the most common type of cancer in the United States. Every day, roughly 9,500 individuals in the United States are diagnosed with skin cancer. Skin cancer is classified into three types: basal cell carcinoma, squamous cell carcinoma, and melanoma.
Melanoma, the deadliest form of skin cancer, develops in the cells that create melanin, the pigment that gives your skin its color. Although the exact cause of all melanomas is unknown, exposure to ultraviolet radiation whether it be from sunlight or elsewhere increases your risk of developing melanoma. Additionally, people who have a lot of moles or abnormal moles are more likely to have skin cancer.
One in every 20,000 newborns is born with a congenital giant nevus, which is a large, pigmented mole that can cover much of the face and body. Because of the appearance of the mole and the potential of it turning into skin cancer in the future, many parents choose to have their children undergo major surgery to remove the whole lesion, which can result in large and permanent scars. Researchers at Massachusetts General Hospital (MGH) have developed multiple preclinical models of this condition and utilized them to demonstrate that several ointments can be applied to the skin to cause the lesions to regress. One topical drug also protected against skin cancer. Their results were published in the journal Cell on May 12th, 2022.
“The goals of our study were to develop a series of animal models designed to elucidate key biological features of these lesions, and to test nonsurgical drug treatments to the skin, aiming to cause the nevus cells to recede, thereby removing the need for surgical treatments,” says senior author David E. Fisher, MD, Ph.D., director of the MGH Cancer Center’s Melanoma Program and director of MGH’s Cutaneous Biology Research Center.
The models included mice modified to express a gene called NRAS, which contains a mutation known to cause most congenital giant nevi in people, as well as mice with transplanted skin grafts containing human congenital giant nevi. Fisher and his colleagues used these models to examine various stages of these nevi in order to better understand how they originate and develop. Furthermore, when the scientists used the animals to evaluate topical applications of single or combination medicines that inhibit signaling pathways known to be triggered by NRAS mutations, they discovered that several of the treatments resulted in significant nevus regressions. Additionally, following three treatments with a drug that triggers a type of inflammatory response after topical administration to the skin, the nevi fully regressed. The treatment also provided complete protection against the formation of skin cancers in mice.
“These findings will hopefully set the stage for additional refinements aimed to directly test such skin treatments on patients with congenital giant nevi,” says Fisher. “This work will include additional studies of safety, potential further enhancements of efficacy, and more analysis of underlying mechanisms. The overall goals are to prevent melanoma in these patients and also to avoid the disfigurement challenges from these lesions.”
Reference: “Topical therapy for regression and melanoma prevention of congenital giant nevi” by Yeon Sook Choi, Tal H. Erlich, Max von Franque, Inbal Rachmin, Jessica L. Flesher, Erik B. Schiferle, Yi Zhang, Marcello Pereira da Silva, Alva Jiang, Allison S. Dobry, Mack Su, Sharon Germana, Sebastian Lacher, Orly Freund, Ezra Feder, Jose L. Cortez, Suyeon Ryu, Tamar Babila Propp, Yedidyah Leo Samuels, Labib R. Zakka, Marjan Azin, Christin E. Burd, Norman E. Sharpless, X. Shirley Liu, Clifford Meyer, William Gerald Austen Jr., Branko Bojovic, Curtis L. Cetrulo Jr., Martin C. Mihm, Dave S. Hoon, Shadmehr Demehri, Elena B. Hawryluk and David E. Fisher, 12 May 2022, Cell.
This work was supported by the National Institutes of Health and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.