A congenital gigantic nevus, a large, pigmented mole that may cover much of the face and body, is present in around one in 20,000 newborns. Many patients choose to have their children have invasive surgery to remove the entire lesion due to the mole’s look and potential of later evolving into skin cancer, which can result in significant and permanent scarring.
Multiple preclinical models of this condition were recently developed and used by researchers at Massachusetts General Hospital (MGH) to demonstrate that several drugs can be applied topically to the skin to cause the lesions to regress, and one topical drug also provided protection against skin cancer.
Their findings are published in the journal Cell.
“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 skin, aiming to cause the nevus cells to recede, thereby removing the need for surgical treatments,” says senior author David E. Fisher, MD, PhD, director of the MGH Cancer Center’s Melanoma Program and director of MGH’s Cutaneous Biology Research Center.
The models included mice that were genetically modified to express the NRAS gene, which has been linked to the majority of congenital large nevi in humans. Other models included mice that received skin grafts from persons that had congenital giant nevi.
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 skin, aiming to cause the nevus cells to recede, thereby removing the need for surgical treatments.
David E. Fisher
To better understand how these nevi form and develop, Fisher and his colleagues used these models to investigate various phases of these nevi.
Additionally, the researchers discovered that some of the treatments resulted in notable nevus regressions when they tested topical applications of single or combinations of medications that disrupt signaling pathways known to be activated by NRAS mutations.
The nevi also completely disappeared after three treatments thanks to a medication that, when applied topically to the skin, triggers an inflammatory response. Additionally, the treatment completely protected mice from developing skin tumors.
“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.”
Additional 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.
The National Institutes of Health and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation supported this work.
