About one in 20,000 infants 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 disease and used them to show that several drugs can be applied to the skin to regress 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 causing nevus cells to recoil, thereby removing the need of surgical treatments. says lead author David E. Fisher, MD, PhD, director of the MGH Cancer Center Melanoma Program and director of MGH’s Cutaneous 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 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 further safety studies, possible further 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 challenges of disfiguring these lesions.
Other study authors include 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, and Elena B. Hawryluk.
This work was supported by the National Institutes of Health and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.
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