Inhibiting Enzyme Reverses Seborrheic Keratosis

A pathway toward non-surgical treatment for the disfiguring skin growths known as seborrheic keratosis (SK) has been discovered by a group of experts at Harvard University and Massachusetts University Hospital (MGH).

These skin lesions are benign but generally seen as an unattractive sign of aging. They are sometimes called "barnacles of life."

Researchers say they are closing in on a treatment.

"Our paper is the first to show that SKs are dependent on an enzyme called Akt for survival," said Victor Neel, MD, PhD, MGH, director of Dermatologic Surgery and lead author of the paper. "Inhibition of this enzyme in SK cells causes rapid cell death while having no effect on normal skin cells. We are confident that this paper heralds the development of an effective, topical treatment for SKs.”

When they pop up on the face or trunk, SKs frequently raise fears of skin cancer for the people who have them. Although structurally related to squamous cell carcinoma (SCC), the SKs are not malignant nor a precursor to skin cancer, according to the paper published online in the Journal of Investigative Dermatology.

However, this research on SKs may advance the attack on skin cancer.

“We hope that a more complete understanding of the benign tumor state will shed light on how cells resist malignant transformation, providing potential insight into the management of life-threatening malignancies,” the scientists said.

The discovery of how Akt inhibitors kill SK cells was serendipitous, according to Neel. The study focused was on why SKs don’t become malignant even though they have some of the same genetic mutations as those found malignant tumors. “We suspect that other yet-to-be-determined mutations in SKs are incompatible with the mutations that lead to malignancy.”

In the past, research on SKs has been hampered by the inability to make cultures from patients’ SK cells, the paper explained. The team developed a method of taking material from biopsied SKs and studying it in the laboratory . They mapped the molecular pathways involved in keeping SK cells alive. As a result, they found that A44, an inhibitor of the Akt enzyme in the SK cells, killed the cells. A44 is among the compounds the team is looking at to develop a topical treatment.