ArticleCell death and differentiation2024
FSP1 inhibition enhances olaparib sensitivity in BRCA-proficient ovarian cancer patients via a nonferroptosis mechanism.
Article in Cell death and differentiation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- HAMNO and CGK733 as BRCAness-driven candidates exhibit synthetic lethality with olaparib in BRCA-proficient ovarian cancer.NPJ precision oncology · 2026Article
- Molecular mechanisms of FSP1-regulated ferroptosis and therapeutic implications in various cancers.Cellular & molecular biology letters · 2026Review
- Salidroside represses ovarian cancer progression by targeting FSP1-dependent ferroptosis.Journal of ovarian research · 2026Article
- PARylation-centric crosstalk: orchestrating immune evasion and multidrug resistance in ovarian cancer.Frontiers in immunology · 2026Review
- Proteasome inhibition induces a BRCAness-like state and sensitises HR-proficient ovarian cancer models to PARP inhibitors.Frontiers in immunology · 2026Article
- Article
- Regulating Ferroptosis in Leukemic Stem Cells: From Stemness Preservation to Targeted Differentiation Strategies.Stem cell reviews and reports · 2026Review
- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- Enhancing PARP inhibitor efficacy in ovarian cancer: targeting the PI3K/AKT/mTOR pathway.Journal of ovarian research · 2025Review
- Ferroptosis meets cancer immunotherapy: Overcoming the crosstalk challenges through advanced drug delivery strategies.Acta pharmaceutica Sinica. B · 2025Review
- Roles and Prospective Applications of Ferroptosis Suppressor Protein 1 (FSP1) in Malignant Tumor Treatment.Current oncology (Toronto, Ont.) · 2025Review
- The Role of Ferroptosis in Women's Health and Diseases.MedComm · 2025Review
- Dual-responsive nanoscale ultrasound contrast agent as an oxidative stress amplifier for enhanced DNA damage in BRCA-proficient ovarian cancer.Materials today. Bio · 2025Article
- Overcoming Ferroptosis-Induced Exhaustion of NK Cells through Inhibition of the ATF3-Mediated Integrated Stress Response in Ovarian Cancer.International journal of biological sciences · 2025Article
- Research progress on ferroptosis and PARP inhibitors in ovarian cancer: action mechanisms and resistance mechanisms.Frontiers in pharmacology · 2025Review
- Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches.Drug design, development and therapy · 2024Review
- Organoids research progress in gynecological cancers: a bibliometric analysis.Frontiers in oncology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
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. Herein, FSP1 is reported to be negatively correlated with the prognosis in OC patients. Combination therapy comprising olaparib and iFSP1 (a FSP1 inhibitor) strongly inhibited tumour proliferation in BRCA-proficient OC cell lines, patient-derived organoids (PDOs) and xenograft mouse models. Surprisingly, the synergistic killing effect could not be reversed by ferroptosis inhibitors, indicating that mechanisms other than ferroptosis were responsible for the synergistic lethality. In addition, cotreatment was shown to induce increased γH2A.X foci and to impair nonhomologous end joining (NHEJ) activity to a greater extent than did any single drug. Mass spectrometry and immunoprecipitation analyses revealed that FSP1 interacted with Ku70, a classical component recruited to and occupying the end of double-strand breaks (DSBs) in the NHEJ process. FSP1 inhibition decreased Ku70 PARylation, impaired subsequent DNA-PKcs recruitment to the Ku complex at DSB sites and was rescued by restoring PARylation. These findings unprecedentedly reveal a novel role of FSP1 in DNA damage repair and provide new insights into how to sensitize OC patients to PARPi treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.