UB researchers identify biomarker and possible new treatment for melanoma

The researchers identified a biomarker and a possible new treatment for melanoma.

The transcription factor badociated with microphthalmia (MITF) is a protein that plays an essential role in maintaining the lineage of melanocytes (cells that make melanin), differentiation of normal and malignant melanocytes, and survival of melanoma cells.

"We have now detected the first useful chemical inhibitor of MITF," said corresponding author, Rhoda Alani, MD, Herbert Mescon's Chair in Dermatology at Boston University School of Medicine.

While genetic mutations in human melanomas have been widely explored in the past decade, the role of epigenetic alterations in the development and progression of melanoma has been less clearly defined.

The researchers found that inhibition of the p300 histone acetyltransferase (HAT) epigenetic enzyme inhibits the growth of human melanoma cells and that cells with increased MITF expression are the most sensitive to this inhibition.

"When human melanoma cell lines were evaluated for their effects on growth using the p300 HAT chemical inhibitor, the most drug-sensitive cell lines were those that expressed High MITF suggesting that MITF expression levels could predict the sensitivity of melanoma to such treatments, "explained Alani, who is also head of dermatology at the Boston Medical Center.

According to the researchers, this inhibitor could have broad implications for the treatment of pigmented lesions of the skin and could possibly be used locally to treat hyperpigmentation.

They hope that this study will provide an incentive to pursue other epigenetic approaches to cancers, both as direct agents targeting specific cancers and as adjunctive therapies to improve responses to cancer immunotherapies.

Philip Cole, MD, Ph.D., professor of medicine, biological chemistry and molecular pharmacology at Harvard University, is also the co-corresponding author.