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Melanoma

Directed therapy

Nature Reviews Cancer volume 13, page 520 (2013)Cite this article

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This paper shows that treatment of melanoma cells with methotrexate (an inhibitor of dihydrofolate reductase (DHFR)) induces the expression of microphthalmia-associated transcription factor (MITF). MITF induces melanocyte differentiation by inducing the transcription of genes, such as tyrosinase (TYR), and inhibits invasive growth. Expression of TYR enables the activation of a prodrug, 3-O-(3,4,5-trimethoxybenzoyl)-(–)-epicatechin (TMECG), which also inhibits DHFR. Combined treatment of melanoma cells with methotrexate and TMECG depletes thymidine pools and induces DNA damage and apoptosis in vivo.

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References

  1. Sáez-Ayala, M. et al. Directed phenotype switching as an effective antimelanoma strategy. Cancer Cell http://dx.doi.org/10.1016/j.ccr.2013.05.009 (2013)

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Authors
  1. Nicola McCarthy
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McCarthy, N. Directed therapy. Nat Rev Cancer 13, 520 (2013). https://doi.org/10.1038/nrc3575

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