ArticleMolecular cancer research : MCR2023
ATF6-Mediated Signaling Contributes to PARP Inhibitor Resistance in Ovarian Cancer.
Article in Molecular cancer research : MCR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Inhibiting CXCR2 Remodels the Tumor Microenvironment and Blunts Tumor Progression and Dissemination of High-Grade Serous Carcinoma.Cancer research communications · 2026Article
- Chromobox 2 Inhibition: A Novel Activity of Alisertib, an Aurora A Kinase Inhibitor.Molecular cancer therapeutics · 2026Article
- Article
- CDK4/6i reverse PARPi resistance by targeting the E2F1- MCM2/5 pathway.NPJ precision oncology · 2026Article
- SM08502-Mediated β-Catenin Repression Synergizes with Olaparib to Inhibit Tumor Progression.Cancer research communications · 2025Article
- The Role of Endoplasmic Reticulum Stress and Unfolded Protein Response in Gynecological Cancers: A Narrative Review.Cureus · 2025Review
- METTL3 overexpression and ATF6 silencing-induced Inhibition in HAS2 expression relieves PDGF-BB stimulation-induced HA production and the proliferation of human orbital fibroblasts in graves' ophthalmopathy.Journal of endocrinological investigation · 2025Article
- Targeting RAD52 overcomes PARP inhibitor resistance in preclinicalbioRxiv : the preprint server for biology · 2025Article
- ATF6 activation promotes tumorigenesis and drug resistance in diffuse large B-cell lymphoma (DLBCL) by regulating the mTOR/S6K signaling pathway.Discover oncology · 2025Article
- Endoplasmic Reticulum Stress: Implications in Diseases.The protein journal · 2025Review
- The Spatial Structure of the Tumor Immune Microenvironment Can Explain and Predict Patient Response in High-Grade Serous Carcinoma.Cancer immunology research · 2024Article
- The Role of Endoplasmic Reticulum Stress on Reducing Recombinant Protein Production in Mammalian Cells.Biochemical engineering journal · 2024Article
- Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma.Cancer research communications · 2024Article
- Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer.Molecular medicine (Cambridge, Mass.) · 2024Review
- CASC4/GOLM2 drives high grade serous carcinoma anoikis resistance through the recycling of EGFR.Cancer gene therapy · 2024Article
- Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy.Cell communication and signaling : CCS · 2024Review
- Establishment and Molecular Characterization of an In Vitro Model for PARPi-Resistant Ovarian Cancer.Cancers · 2023Article
- Unfolded protein response complexity in gynecological tumor dynamics: therapeutic challenges and future perspectives.Cell cycle (Georgetown, Tex.)Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
High-grade serous ovarian cancer (HGSOC) is the deadliest ovarian cancer histotype due in-part to the lack of therapeutic options for chemotherapy-resistant disease. PARP inhibitors (PARPi) represent a targeted treatment. However, PARPi resistance is becoming a significant clinical challenge. There is an urgent need to overcome resistance mechanisms to extend disease-free intervals. We established isogeneic PARPi-sensitive and -resistant HGSOC cell lines. In three PARPi-resistant models, there is a significant increase in AP-1 transcriptional activity and DNA repair capacity. Using RNA-sequencing and an shRNA screen, we identified activating transcription factor 6 (ATF6) as a mediator of AP-1 activity, DNA damage response, and PARPi resistance. In publicly available datasets, ATF6 expression is elevated in HGSOC and portends a poorer recurrence-free survival. In a cohort of primary HGSOC tumors, higher ATF6 expression significantly correlated to PARPi resistance. In PARPi-resistant cell lines and a PDX model, inhibition of a known ATF6 regulator, p38, attenuated AP-1 activity and RAD51 foci formation, enhanced DNA damage, significantly inhibited tumor burden, and reduced accumulation of nuclear ATF6. IMPLICATIONS: This study highlights that a novel p38-ATF6-mediated AP-1 signaling axis contributes to PARPi resistance and provides a clinical rationale for combining PARPi and AP-1 signaling inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
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.