Supplementary Figure S1-S7 from BRCA1-Mediated Dual Regulation of Ferroptosis Exposes a Vulnerability to GPX4 and PARP Co-Inhibition in BRCA1-Deficient Cancers

Supplementary Figure S1 shows that BRCA1 deficiency promotes GPX4i–induced ferroptosis. Supplementary Figure S2 shows that BRCA1 regulates GPX4 through the BRCT domain. Supplementary Figure S3 shows that BRCA1 deficiency suppresses erastin-induced ferroptosis via interference with VDAC3 transcription and mitochondrial lipid peroxidation.Supplementary Figure S4 shows that PARPi synergize with GPX4i in BRCA1-deficient cancers via ferroptosis. Supplementary Figure S5 shows that PARPi combined with GPX4i in BRCA1-mutant/deficient or homologous-recombination-restored cells or tumors. Supplementary Figure S6 shows that NCOA4-mediated ferritinophagy coupled with defective GPX4 induction contributes to the synergy of PARPi and GPX4i in BRCA1-deficient cancer cells. Supplementary Figure S7 shows that GPX4i overcome resistance to PARPi in BRCA1-mutant tumors.