FSP1 inhibition enhances olaparib sensitivity in BRCA-proficient ovarian cancer patients via a nonferroptosis mechanism
Huixian Miao,
Huangyang Meng,
Yashuang Zhang
et al.
Abstract:Poly ADP-ribose polymerase inhibitors (PARPis) exhibit promising efficacy in patients with BRCA mutations or homologous repair deficiency (HRD) in ovarian cancer (OC). However, less than 40% of patients have HRD, it is vital to expand the indications for PARPis in BRCA-proficient patients. Ferroptosis suppressor protein 1 (FSP1) is a key protein in a newly identified ferroptosis-protective mechanism that occurs in parallel with the GPX4-mediated pathway and is associated with chemoresistance in several cancers… Show more
“…Inhibition of FSP1 blocks the antioxidant effects of the FSP1-CoQ10-NAD(P)H pathway, thereby inducing ferroptosis. 40 …”
Section: Ferroptosis Mechanismmentioning
confidence: 99%
“…The FSP1-CoQ10-NAD(P)H pathway and the GSH-GPX4 pathway are two parallel lipid antioxidant pathways. 40 CoQ10 (ubiquinone) is a lipophilic free radical trapping antioxidant that blocks the propagation of lipid peroxides and inhibits ferroptosis. 41 Its reduced form of CoQ10H2 (panthenol) reduces oxidative stress and inhibits lipid ROS accumulation.…”
“…Inhibition of FSP1 blocks the antioxidant effects of the FSP1-CoQ10-NAD(P)H pathway, thereby inducing ferroptosis. 40 …”
Section: Ferroptosis Mechanismmentioning
confidence: 99%
“…The FSP1-CoQ10-NAD(P)H pathway and the GSH-GPX4 pathway are two parallel lipid antioxidant pathways. 40 CoQ10 (ubiquinone) is a lipophilic free radical trapping antioxidant that blocks the propagation of lipid peroxides and inhibits ferroptosis. 41 Its reduced form of CoQ10H2 (panthenol) reduces oxidative stress and inhibits lipid ROS accumulation.…”
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