Researchers have shown that a topical version of a melanoma drug can accelerate healing of skin wounds—a discovery that has significant potential for treatment of chronic wounds, surgical incisions, and more, according to the authors of a study published August 1, 2016 in the journal Nature Communications.
Researchers realized that hyperproliferative skin conditions occur as a side effect of BRAF inhibitors, which are highly effective therapies for the treatment of melanoma in BRAF-positive patients. These hyperproliferative skin changes are caused by the paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells.
“We set out to take advantage of our mechanistic understanding of these drugs and see if we could turn a side effect into a potentially beneficial effect,” said senior author Antoni Ribas, MD, PhD, Director of the UCLA Jonsson Comprehensive Cancer Center Tumor Immunology Program, in Los Angeles, CA.
“These agents have great potential to be used to develop topical treatments to greatly accelerate wound healing,” Dr. Ribas added.
The prevalence rate of chronic wounds is high—similar to that of heart failure. Chronic wounds affect more than 6.5 million Americans and cost an estimated $50 billion to treat. These numbers are only expected to worsen with increasing rates of diabetes and obesity.
“Finding a cure for acute and chronic wounds remains a worldwide challenge,” said the study’s first author Helena Escuin-Ordinas, PhD. “Topical BRAF inhibitors hold great promise to promote skin recovery, not only after injury such as from abrasions, ulcers, or surgery, but in skin-related side effects that result from treatment for a wide variety of diseases, such as cancer and diabetes, where current therapies are not highly effective.”
Dr. Escuin-Ordinas and colleagues in Dr. Ribas’ lab hypothesized that inducing paradoxical MAPK activation in keratinocytes could accelerate cutaneous wound healing. The investigators performed experiments in human cultures and in two mouse models to test this idea.
Using a topical version of BRAF inhibitor vemurafenib (Zelboraf), the researchers demonstrated that the drug accelerated the healing of skin wounds (by primarily acting on the proliferative stage of wound healing) without promoting skin carcinogenesis.
In light of these initial results, the researchers plan to develop pre-clinical models to further study these mechanisms, with the hope of beginning clinical studies of topical BRAF treatments in the near future, Dr. Ribas said.
He and Dr. Escuin-Ordinas have also obtained a patent for the use of topical BRAF inhibitors for wound healing, which has been licensed to Lutris Pharma.