ArticleOncogene2021
Combined inhibition of DDR1 and CDK4/6 induces synergistic effects in ER-positive, HER2-negative breast cancer with PIK3CA/AKT1 mutations.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 19 citations in OpenAlex.
- The DDR1 Tyrosine Kinase Promotes Th17 Cell Migration in Three-Dimensional Collagen and into the Joints During Inflammatory Arthritis.International journal of molecular sciences · 2026Article
- Next-generation sequencing methodologies to identify patients for targeted therapy: focus on HR+/HER2- metastatic breast cancer.Pathologica · 2025Review
- Discoidin Domain Receptors in Tumor Biology and Immunology: Progression and Challenge.Biomolecules · 2025Review
- TFAP2C-DDR1 axis regulates resistance to CDK4/6 inhibitor in breast cancer.Cancer letters · 2025Article
- Sparstolonin B Reduces Estrogen-Dependent Proliferation in Cancer Cells: Possible Role of Ceramide and PI3K/AKT/mTOR Inhibition.Pharmaceuticals (Basel, Switzerland) · 2024Article
- DDR1 is identified as an immunotherapy target for microsatellite stable colon cancer by CRISPR screening.NPJ precision oncology · 2024Article
- Review
- Secretome Analysis Using Affinity Proteomics and Immunoassays: A Focus on Tumor Biology.Molecular & cellular proteomics : MCP · 2024Review
- Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.Journal of translational medicine · 2024Review
- Euphorbia factor L1 suppresses breast cancer liver metastasis via DDR1-mediated immune infiltration.Aging · 2023Article
- RAGE inhibition blunts insulin-induced oncogenic signals in breast cancer.Breast cancer research : BCR · 2023Article
- A pan-cancer analysis of DDR1 in prognostic signature and tumor immunity, drug resistance.Scientific reports · 2023Article
- Collagen Remodeling along Cancer Progression Providing a Novel Opportunity for Cancer Diagnosis and Treatment.International journal of molecular sciences · 2022Review
- Preclinical evaluation of proteolytic targeting of LCK as a therapeutic approach in T cell acute lymphoblastic leukemia.Science translational medicine · 2022Article
- Discoidin domain receptor 1a (DDR1a) confers 5-fluorouracil cytotoxicity in LoVo cell via PI3K/AKT/Bcl-2 pathway.Bioengineered · 2022Article
- RNA interference screens discover proteases as synthetic lethal partners of PI3K inhibition in breast cancer cells.Theranostics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Molecular alterations in the PI3K/AKT pathway occur frequently in hormone receptor-positive breast tumors. Patients with ER-positive, HER2-negative metastatic breast cancer are often treated with CDK4/6 inhibitors such as palbociclib in combination with endocrine therapy. Although this is an effective regimen, most patients ultimately progress. The purpose of this study was identifying synthetic lethality partners that can enhance palbociclib's antitumor efficacy in the presence of PIK3CA/AKT1 mutations. We utilized a barcoded shRNA library to determine critical targets for survival in isogenic MCF7 cells with PIK3CA/AKT1 mutations. We demonstrated that the efficacy of palbociclib is reduced in the presence of PIK3CA/AKT1 mutations. We also identified that the downregulation of discoidin domain receptor 1 (DDR1) is synthetically lethal with palbociclib. DDR1 knockdown and DDR1 pharmacological inhibitor decreased cell growth and inhibited cell cycle progression in all cell lines, while enhanced the sensitivity of PIK3CA/AKT1 mutant cells to palbociclib. Combined treatment of palbociclib and 7rh further induced cell cycle arrest in PIK3CA/AKT1 mutant cell lines. In vivo, 7rh significantly enhanced palbociclib's antitumor efficacy. Our data indicates that DDR1 inhibition can augment cell cycle suppressive effect of palbociclib and could be effective strategy for targeted therapy of ER-positive, HER2-negative breast cancers with PI3K pathway activation.
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.