Sunday, November 5, 2017

Copper Chelation to inhibit BRAF V600E melanoma growth and decrease resistance to BRAF/MEK inhibitors???

I've actually reported on Copper Chelation and melanoma before.  Here is this from 2015:  CDK4/6 inhibitors, PLX8394, or copper chelation?????

Now there's this:

Copper Chelation Inhibits BRAFV600E-driven Melanomagenesis and Counters Resistance to BRAFV600E and MEK1/2 Inhibitors. Counter, Crowe, Greenberg and Brady.  Cancer Res. 2017 Oct 6.
MEK1/2 and BRAFV600E inhibitors are used to treat BRAFV600E-positive melanoma, with other cancers under evaluation. Genetic perturbation of copper import or pharmacological reduction of copper with the clinical copper chelator TTM inhibits MEK1/2 kinase activity and reduces BRAFV600E-driven tumorigenesis. In this study, we report that TTM inhibited transformed growth of melanoma cell lines resistant to BRAF or MEK1/2 inhibitors and enhanced the antineoplastic activity of these inhibitors. TTM also provided a survival advantage in a genetically engineered mouse model of melanoma, and when accounting for putative overdosing, trended towards an increase in the survival benefit afforded by BRAF inhibition. This effect was phenocopied by genetically inhibiting copper import in tumors, which was linked to a reduction in MAPK signaling. Thus, TTM reduces copper levels and MAPK signaling, thereby inhibiting BRAFV600E-driven melanoma tumor growth. These observations inform and support clinical evaluation of TTM in melanoma.

Sounds good to me!  Hang in there ratties!  -  c

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