Potential topical Tx for giant congenital nevi


Giant congenital melanocytic naveus. Photo by: Mohammad2018 via Wikimedia Commons

Early research suggests it may be possible to treat giant congenital melanocytic nevi in children with a topical approach, rather than a surgical one.


These findings come from a paper published in Cell (May 12, 2022).


In a press release from Massachusetts General Hospital (MGH), where the research was conducted, the investigators note that approximately one in 20,000 infants is born with a congenital giant nevus—a huge, pigmented mole that may cover up to 80% of the face and body.


Many parents decide to have these moles removed, due to the elevated risk of skin cancer they represent as well as for aesthetic reasons. However, at this time removing the lesions requires extensive surgery that can leave large, permanent scars.


This new paper investigates several topical approaches to shrinking these lesions in preclinical models.


“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,” said senior author David E. Fisher, MD, PhD, in the release. Dr. Fisher is director of the MGH Cancer Center’s Melanoma Program and director of MGH’s Cutaneous Biology Research Center.


Both genetically modified animals and animals with human congenital giant nevi xenografts were used.


The investigators found that cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions of lesions. SADBE, in particular, triggered an innate immune response that fully prevented melanoma and shrank grafted human lesions.


“These findings will hopefully set the stage for additional refinements aimed to directly test such skin treatments on patients with congenital giant nevi,” said Dr. 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.”

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