Summary of study ST001339

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000915. The data can be accessed directly via it's Project DOI: 10.21228/M8DQ2M This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001339
Study TitleDisruption of Redox Balance Enhances the Effects of BRAF-inhibitors in Melanoma
Study SummarySpecifically, we report that drug-insensitive melanoma cells can maintain higher levels of antioxidant metabolites to withstand the lethal effects of drugs. By extending our analysis to other melanoma subtypes in the TCGA, we show that elevated redox capacity could indeed be a general feature of melanoma. Our results suggest that redox vulnerabilities could be exploited for therapeutic benefits and identify unsuspected combination targets to enhance the effects of BRAFi in pan-melanoma.
Institute
Vanderbilt University
Last NameCodreanu
First NameSimona
Address1234 Stevenson Center Lane
Emailsimona.codreanu@vanderbilt.edu
Phone6158758422
Submit Date2020-03-31
Raw Data AvailableYes
Raw Data File Type(s).raw
Analysis Type DetailLC-MS
Release Date2021-03-31
Release Version1
Simona Codreanu Simona Codreanu
https://dx.doi.org/10.21228/M8DQ2M
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000915
Project DOI:doi: 10.21228/M8DQ2M
Project Title:Disruption of Redox Balance Enhances the Effects of BRAF-inhibitors in Melanoma
Project Type:Untargeted-Targeted Metabolomics analysis
Project Summary:Melanomas harboring BRAF mutations can be treated with BRAF inhibitors, but tumor recurrence is inevitable. In spite of large-scale attempts, there remains an unmet need to uncover molecular determinants of BRAFi insensitivity and devise actionable combination targets to overcome resistance. Here, using an integrative approach of experimentation, and mathematical flux balance analyses in a panel of BRAF-mutated melanoma cells, we show that elevated antioxidant capacity of melanoma cells is linked to their drug sensitivity. Specifically, we report that drug-insensitive melanoma cells can maintain higher levels of antioxidant metabolites to withstand the lethal effects of drugs. By extending our analysis to other melanoma subtypes in the TCGA, we show that elevated redox capacity could indeed be a general feature of melanoma. Our results suggest that redox vulnerabilities could be exploited for therapeutic benefits and identify unsuspected combination targets to enhance the effects of BRAFi in pan-melanoma.
Institute:Vanderbilt University
Last Name:Codreanu
First Name:Simona
Address:1234 Stevenson Center Lane
Email:simona.codreanu@vanderbilt.edu
Phone:6158758422
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