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MITF identified as therapeutic target in melanoma

New research suggests that the protein microphtalmia-associated transcription factor (MITF), which plays a role in the maintenance of cells of the melanocyte lineage and the differentiation and survival of malignant melanocytes, could be a therapeutic target for melanoma treatment.

The findings come from a paper published online ahead of print in Cancer Research (Mar. 25, 2019).

“We have now detected the first useful chemical inhibitor of MITF,” said Dr. Rhoda Alani, in a press release from the Boston University School of Medicine.

Dr. Alani, the corresponding author on the paper, is the Herbert Mescon Chair of Dermatology at the university and chief of dermatology at Boston Medical Center.

In the release, the authors note that epigenetic factors have received less attention than mutation for their potential role in the the development and progression of melanoma.

They found that inhibiting the epigenetic p300 Histone Acetyltransferase (HAT) enzyme prevented growth of human melanoma cells, and that cells with increased expression of MITF were most sensitive to this inhibition.

“When human melanoma cell lines were evaluated for growth effects using the chemical inhibitor of p300 HAT, the cell lines that were most sensitive to drug treatment were those that expressed high levels of oMITF, suggesting that MITF expression levels can predict melanoma sensitivity to such therapies,” said Dr. Alani.

The researchers suggest this p300 HAT inhibitor may have broad implications for the treatment of pigmented lesions in the skin—potentially being used topically to treat hyperpigmentation.

Dr. Alani and her colleagues hope their study findings will provide incentive to pursue additional epigenetic approaches to cancers, both ad direct agents targeting specific cancers and as adjuvant therapies to improve response to immunotherapies.

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