A new treatment may help reverse giant congenital nevi
Skin cancer is the most common type of cancer in the United States. Every day, approximately 9,500 people in the United States are diagnosed with skin cancer. Skin cancer is divided into three types: basal cell carcinoma, squamous cell carcinoma and melanoma.
Melanoma, the deadliest form of skin cancer, develops in the cells that produce melanin, the pigment that gives your skin its color. Although the exact cause of all melanomas is unknown, exposure to ultraviolet radiation, whether from sunlight or elsewhere, increases your risk of developing melanoma. In addition, people with many moles or abnormal moles have a higher risk of developing skin cancer.
One in 20,000 newborns is born with a giant congenital nevus, which is a large, pigmented birthmark that can cover much of the face and body. Because of the birthmark’s appearance and the possibility that it may develop into skin cancer in the future, many parents choose to have their children have major surgery to remove the entire lesion, which can result in large and permanent scars. Researchers at Massachusetts General Hospital (MGH) have developed several preclinical models of this condition and used them to show that several ointments can be applied to the skin to induce lesion regression. A topical drug also protected against skin cancer. Their results were published in the journal cell on May 12, 2022.
“The objectives of our study were to develop a series of animal models to elucidate the main biological features of these lesions and to test non-surgical drug treatments of the skin with the aim of inducing the nevus cells to retreat and thereby eliminating 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 the 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 giant congenital nevi in humans, and mice with transplanted skin grafts containing human giant congenital nevi. Fisher and his colleagues used these models to study different stages of these nevi to better understand how they form and develop. When the scientists also used the animals to evaluate topical applications of single or combination drugs that inhibit signaling pathways known to be triggered by NRAS mutations, they found that several of the treatments resulted in significant nevus regressions. In addition, the nevi completely regressed after three treatments with a drug that triggers a type of inflammatory response when applied topically to the skin. The treatment also provided complete protection against skin cancer formation in mice.
“Hopefully, these results will set the stage for further refinements aimed at testing such skin treatments directly on patients with giant congenital nevi,” says Fisher. “This work will include additional safety studies, potential further improvements in efficacy and further analysis of the underlying mechanisms. The overall goal is to prevent melanoma in these patients and also avoid the challenges of disfiguring these lesions.”
Reference: “Topical Therapy for Regression and Melanoma Prevention of Giant Congenital 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, May 12, 2022 Cell.
This work was supported by the National Institutes of Health and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.