ArticleCancer cell2018
BRD4 Inhibition Is Synthetic Lethal with PARP Inhibitors through the Induction of Homologous Recombination Deficiency.
2 registry-linked trialsOpen access · bronzeAbstract read
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Article in Cancer cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 177 papers.
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177citing papers in PubMed
13.0field-weighted citation impact, top 1% of its field
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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.
Randomized, Open, Controlled, Multicenter Phase III Clinical Study of Fluzoparib in Combination With Apatinib Versus Investigator-Selected Chemotherapy for HRD-Positive/HER2-negative Advanced Breast Cancer
NCT07371910 phase3active not recruitingnot on this mapstarted 2024, after this paper: background citation
A Randomized, Open-label, Controlled, Multicenter Phase III Study of Fluorizoparib in Combination With Apatinib Versus Investigator's Choice Chemotherapy in Patients With HRD-positive, HER2-negative Advanced Breast Cancer
Who cites it
177 citing papers in PubMed, 298 citations in OpenAlex.
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Mitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- PROTAC-based nanoassemblies targeting BRD4 for potentiate FLASH radiosensitization therapy.Materials today. Bio · 2026Article
- BET inhibition unmasks a targetable glycolytic dependency through a HIF1α stabilization and driven transcriptional program in a defined subset of triple-negative breast Cancer.Cell death discovery · 2026Article
- PAK1 inhibition synergistically enhances the anti-tumor efficacy of PARP inhibitors in ovarian cancers.Genes & diseases · 2026Article
- Overcoming Resistance in Triple-Negative Breast Cancer: A Translational Perspective on Next-Generation DNA Damage Response Inhibitors and Synthetic Lethality.Molecules (Basel, Switzerland) · 2026Review
- KAT2B-mediated epigenetic suppression of RAD51C enhances olaparib sensitivity in colorectal cancer.Cancer chemotherapy and pharmacology · 2026Article
- BET inhibition disrupts the FOXM1-MYC axis to induce BRCAness and enhance PARP inhibitor response.NPJ precision oncology · 2026Article
- Improving PARP inhibitor efficacy in bladder cancer without genetic BRCAness by combination with PLX51107.Molecular oncology · 2026Article
- PROTAC-based synthetic lethality strategy endogenously activates systemic STING to boost antitumor immunity.Science advances · 2026Article
- Exploiting synthetic lethality in epithelial ovarian cancer: multi-dimensional approaches beyond DNA damage repair.Molecular cancer · 2026Review
- Exploring the optimal cutoff point and genomic characteristics for PARP inhibitor maintenance therapy in early recurrence of ovarian cancer.Journal of ovarian research · 2026Article
- Article
- Chromatin adaptation and histone remodeling as mechanisms of PARP inhibitor resistance and therapeutic vulnerability.Frontiers in pharmacology · 2026Review
- Article
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- Design and Development of DNA Damage Chemical Inducers of Proximity (DD-CIP) for Targeted Cancer Therapy.bioRxiv : the preprint server for biology · 2025Article
- BRD9-p53-E2F1 circuit orchestrates cell growth and DNA damage repair in gastric cancer.Molecular cancer · 2025Article
- Automated machine learning profiling with MAP-HR for quantifying homologous recombination foci in patient samples.NAR cancer · 2025Article
117 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 3 countries.
Chaoyang SunDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: suncydoctor@gmail.com.
Jun YinDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Aurora Research Institute, Milwaukee, WI 53202, USA.
Yong FangDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jian ChenDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310000, China.
Kang Jin JeongDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Xiaohua ChenDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Christopher P VellanoDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Zhenlin JuDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Wei ZhaoDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Dong ZhangDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yiling LuDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Funda Meric-BernstamDepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Timothy A YapDepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Maureen HattersleyIMED Oncology, AstraZeneca, 35 Gatehouse Drive, Waltham, MA 02451, USA.
Mark J O'ConnorAstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0RE, UK.
Huawei ChenIMED Oncology, AstraZeneca, 35 Gatehouse Drive, Waltham, MA 02451, USA.
Stephen FawellIMED Oncology, AstraZeneca, 35 Gatehouse Drive, Waltham, MA 02451, USA.
Shiaw-Yih LinDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Guang PengDepartment of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Gordon B MillsDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
The University of Texas MD Anderson Cancer Center · USAstraZeneca (United States) · USAstraZeneca (United Kingdom) · GBAurora Health Care · USHuazhong University of Science and Technology · CNSecond Affiliated Hospital of Zhejiang University · CNTongji Hospital · CN
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MUNIVERSITY OF TEXAS MD ANDERSON SPORE IN OVARIAN CANCERP50CA083639 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BAST, ROBERT C · 1999 to 2015
$33.0MTargeting the PI3K Signaling Pathway in Endometrial CarcinomaP50CA098258 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BODURKA, DIANE · 2003 to 2020
$32.0MU.T. M. D. Anderson Cancer Center SPORE in Ovarian CancerP50CA217685 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SOOD, ANIL K · 2017 to 2021
$7.9MBiological annotation of TCGA dataU01CA168394 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MILLS, GORDON B. · 2012 to 2016
$4.7MIntegrative bioinformatics and functional characterization of oncogenic driver aberrations in cancerU01CA217842 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DENEEN, BENJAMIN, MILLS, GORDON B. · 2017 to 2021
$3.6MThe Role of Aberrant Splicing of EVl1 in Ovarian Cancer PathophysiologyR01CA123219 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MILLS, GORDON B., NANJUNDAN, MEERA · 2008 to 2012
$2.2MIntegrated analysis of protein expression data from the Reverse Phase Protein Array (RPPA) platformU24CA210950 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AKBANI, REHAN, MILLS, GORDON B. · 2016 to 2020
$1.8MFunctional Proteomics by Reverse Phase Protein Array in CancerR50CA221675 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LU, YILING · 2017 to 2021
$726kNCI NIH HHS P30 CA016672NCI NIH HHS P50 CA083639NCI NIH HHS P50 CA098258NCI NIH HHS P50 CA217685NCI NIH HHS R50 CA221675NCI NIH HHS U01 CA168394NCI NIH HHS U01 CA217842NCI NIH HHS U24 CA210950
Abstract
Poly(ADP-ribose) polymerase inhibitors (PARPi) are selectively active in cells with homologous recombination (HR) deficiency (HRD) caused by mutations in BRCA1, BRCA2, and other pathway members. We sought small molecules that induce HRD in HR-competent cells to induce synthetic lethality with PARPi and extend the utility of PARPi. We demonstrated that inhibition of bromodomain containing 4 (BRD4) induced HRD and sensitized cells across multiple tumor lineages to PARPi regardless of BRCA1/2, TP53, RAS, or BRAF mutation status through depletion of the DNA double-stand break resection protein CtIP (C-terminal binding protein interacting protein). Importantly, BRD4 inhibitor (BRD4i) treatment reversed multiple mechanisms of resistance to PARPi. Furthermore, PARPi and BRD4i are synergistic in multiple in vivo models.
Indexed as
AnimalsBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorDNA DamageDNA RepairFemaleHomologous RecombinationHumansMice, TransgenicMutationNuclear ProteinsOvarian NeoplasmsPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesTranscription FactorsBRD4 protein, humanBrd4 protein, mouseBromodomain Containing ProteinsCell Cycle ProteinsNuclear ProteinsPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesTranscription FactorsBRD4 inhibitorCtBP-interacting proteinCtIPhomologous recombinationPARP inhibitor
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Registered trials
NCT06255392ClinicalTrials.gov
NCT07371910ClinicalTrials.gov
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.