Dual Targeting of BRAF-V600E and Ferroptosis Results in Synergistic Anticancer Activity via Iron Overload and Enhanced Oxidative Stress (EORTC-NCI-AACR 2024) - Sep 8, 2024 - Abstract #219; PB207; Pres time: Oct 24, 2024; 09:00 AM - 05:30 PM; Location: Exhibition Hall; "We hypothesized that combination BRAF inhibition and ferroptosis induction will have synergistic/additive anticancer activity in BRAFV600E-mutant ATC. We performed in vitro, ex vivo and in vivo studies to evaluate the effects of BRAF inhibition combined with ferroptosis induction to determine the anticancer effects and underlying mechanism of action of combination treatment in ATC. Targeting key regulators of ferroptosis [GPX4 (using RSL3 and ML162) and System Xc− (via erastin)] induced significant cell death in all four ATC cell lines (2 BRAFWT, 2 BRAFV600E-mutant)...Combining dabrafenib (BRAF inhibitor) with RSL3 synergistically increased cell death in BRAFV600E-mutant ATC cell lines but not wild type as expected... Our results show that dual targeting of BRAFV600E and ferroptosis in ATC results in synergistic anticancer activity due to iron overload, Fenton's reaction and oxidative stress. This dual-targeting treatment strategy may overcome acquired BRAF..."
Oxidative stress • Endocrine Cancer • Melanoma • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF • GPX4
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J. Hu 1; C. Ghosh 1; T. Pal 1; Z. Yang 1; S. Dixon 2; E. Kebebew 1
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