Discovery of 4 subtypes of melanoma points to new treatment approaches
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FINDINGS

Melanoma, a relatively rare but deadly skin cancer, has been shown to switch differentiation states — that is, to regress to an earlier stage of development — which can lead it to become resistant to treatment. Now, UCLA researchers have found that melanomas can be divided into four distinct subtypes according to their stages of differentiation. Cell subtypes that de-differentiated — meaning that they reverted back to a less-mature cell — showed sensitivity to a type of self-inflicted cell death called ferroptosis.

The research also showed that certain subtypes of melanoma cells could be successfully treated using multiple cancer therapies in combination with ferroptosis-inducing drugs.

BACKGROUND

Melanoma arises from melanocytes, cells that produce pigments. Although targeted therapies and a greater understanding of cancer immunology have significantly improved survival, many patients either relapse or do not respond to treatment.

METHOD

The UCLA team, led by Dr. Thomas Graeber, analyzed the gene expression of melanoma cells and compared them to information in public genetic databases to identify the four different subtypes of melanoma with different drug sensitivities. The team organized the melanoma cells according to characteristic patterns of genes turned on by the cells. Comparing the gene expression patterns to

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