Discovery of therapeutic targets for melanoma


A study led by a professor of dermatology at Boston University School of Medicine Herbert Mescon has shown that they have identified a biomarker and a possible new treatment for melanoma. These findings were published in the online journal cancer research.

Melanoma is derived from the spinal nerve melanocytes and is one of the most aggressive malignant tumors. Melanoma is caused by excessive proliferation of abnormal melanocytes. Melanocytes are skin cells that produce melanin, a brown pigment that imparts color to the skin and protects the inner layers of the skin from the sun.

Melanoma often occurs in the mucous membranes of the skin or adjacent to the skin, as well as in the perichondrium and choroid. Although the incidence rate is low, the degree of malignancy is high, the metastasis is early, and the mortality rate is high. Unfortunately, there are currently no effective treatments to block melanoma metastasis. Therefore, scientists have been studying melanoma and hope to find a way to prevent or treat it.

MITF (Microphthalmia-associated transcription factor) is not only a major regulatory protein for melanocyte growth, differentiation and pigmentation, but also plays an important role in the malignant transformation of melanocytes and the occurrence, development, and metastasis of melanoma. MITF plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1).

Previous studies have demonstrated that MITF has a dual role in melanoma. On the one hand, MITF is a melanoma proto-oncogene gene with the ability to promote tumor proliferation; on the other hand, MITF is the most important differentiation marker of melanocytes, which is negatively correlated with tumor invasion ability and has certain anti-tumor activity.

Although genetic mutations in human melanoma have been extensively explored over the past decade, the role of epigenetic changes in the development and progression of melanoma remains unclear.

The researchers found that inhibition of epigenetic p300 HAT (p300 histone acetyltransferase) inhibited the growth of human melanoma cells. When using the chemical inhibitors of p300 HAT to assess the growth effects of human melanoma cell lines, the most sensitive cell lines for drug therapy are those that express high levels of MITF, indicating that MITF expression levels can predict the sensitivity of melanoma to these treatments.

They believed that this inhibitor may affect the treatment of pigmented skin lesions extensively, and may also be used locally to treat hyperpigmentation.

The researchers hope that their study will provide an additional epigenetic approach to cancers-- it can be used as a direct drug for specific cancers or as an adjunct to improve response to cancer immunotherapy.
 
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