ArticleProceedings of the National Academy of Sciences of the United States of America2015
Selective resistance to the PARP inhibitor olaparib in a mouse model for BRCA1-deficient metaplastic breast cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Comparative oncogenomics identifies combinations of driver genes and drug targets in BRCA1-mutated breast cancer.Nature communications · 2019Pooled it
- Trial
- PARP1-selective inhibitor DSB1559 demonstrates superior efficacy and antitumor immunity in triple-negative breast cancer.Journal for immunotherapy of cancer · 2026Article
- Decoding PARP roles in breast cancer therapy resistance.Molecular biology reports · 2026Review
- PARP inhibitor-induced anti-tumour chemokine response is suppressed by dipeptidyl peptidase 4 (DPP4) in ovarian cancer.British journal of cancer · 2025Article
- From lab to life: technological innovations in transforming cancer metastasis detection and therapy.Discover oncology · 2025Review
- Molecular Targets for Pharmacotherapy of Head and Neck Squamous Cell Carcinomas.Current issues in molecular biology · 2025Review
- Enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancer.NPJ breast cancer · 2025Article
- BRCA1 and BRCA2 as prognostic markers in oral squamous cell carcinoma: a minireview.Frontiers in oncology · 2025Review
- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.Nature communications · 2024Article
- FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.EMBO molecular medicine · 2024Article
- Article
- Advances in Making Cancer Mouse Models More Accessible and Informative through Non-Germline Genetic Engineering.Cold Spring Harbor perspectives in medicine · 2024Review
- Metaplastic Carcinoma of the Breast: Case Series of a Single Institute and Review of the Literature.Medical sciences (Basel, Switzerland) · 2023Review
- Review
- Exploiting Cancer Synthetic Lethality in Cancer-Lessons Learnt from PARP Inhibitors.Cancer treatment and research · 2023Article
- PARP inhibitors in metastatic prostate cancer.Frontiers in oncology · 2023Review
- DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.International journal of molecular sciences · 2022Review
- Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Metaplastic breast carcinoma (MBC) is a rare histological breast cancer subtype characterized by mesenchymal elements and poor clinical outcome. A large fraction of MBCs harbor defects in breast cancer 1 (BRCA1). As BRCA1 deficiency sensitizes tumors to DNA cross-linking agents and poly(ADP-ribose) polymerase (PARP) inhibitors, we sought to investigate the response of BRCA1-deficient MBCs to the PARP inhibitor olaparib. To this end, we established a genetically engineered mouse model (GEMM) for BRCA1-deficient MBC by introducing the MET proto-oncogene into a BRCA1-associated breast cancer model, using our novel female GEMM ES cell (ESC) pipeline. In contrast to carcinomas, BRCA1-deficient mouse carcinosarcomas resembling MBC show intrinsic resistance to olaparib caused by increased P-glycoprotein (Pgp) drug efflux transporter expression. Indeed, resistance could be circumvented by using another PARP inhibitor, AZD2461, which is a poor Pgp substrate. These preclinical findings suggest that patients with BRCA1-associated MBC may show poor response to olaparib and illustrate the value of GEMM-ESC models of human cancer for evaluation of novel therapeutics.
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.