PT  - JOURNAL ARTICLE
AU  - B. Bishal Paudel
AU  - Joshua E. Lewis
AU  - Keisha N. Hardeman
AU  - Corey E. Hayford
AU  - Charles J. Robbins
AU  - Simona G. Codreanu
AU  - Stacy D. Sherrod
AU  - John A. McLean
AU  - Melissa L. Kemp
AU  - Vito Quaranta
TI  - Disruption of Redox Balance Enhances the Effects of BRAF-inhibition in Melanoma Cells
AID  - 10.1101/818989
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 818989
4099  - http://biorxiv.org/content/early/2019/10/28/818989.short
4100  - http://biorxiv.org/content/early/2019/10/28/818989.full
AB  - Summary Melanomas harboring BRAF mutations can be treated with BRAF inhibitors (BRAFi), but responses are varied and tumor recurrence is inevitable. Here, using an integrative approach of experimentation and mathematical flux balance analyses in BRAF-mutated melanoma cells, we report that elevated antioxidant capacity is linked to BRAFi sensitivity in melanoma cells. High levels of antioxidant metabolites in cells with reduced BRAFi sensitivity confirm this conclusion. By extending our analyses to other melanoma subtypes in TCGA, we predict that elevated redox capacity is a general feature of melanomas, not previously observed. We propose that redox vulnerabilities could be exploited for therapeutic benefits and identify unsuspected combination targets to enhance the effects of BRAFi in any melanoma, regardless of mutational status.