ArticleCell cycle (Georgetown, Tex.)2012
Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04360941 (PAveMenT), which is not on this map. Cited by 134 papers.
What it found
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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.
PAveMenT: Phase Ib Study of Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer
Who cites it
134 citing papers in PubMed, 226 citations in OpenAlex.
- Trial
- Review
- Next Frontier in HER2+/HR+ Breast Cancer: Leveraging Cell Cycle Control with CDK4/6 Inhibitors.Journal of personalized medicine · 2026Review
- Cyclin-Dependent 4/6 Kinase Inhibitors for Treatment of HER2-Positive Breast Cancer: 2026 Update.Cancers · 2026Review
- CRYβB2 is a biomarker for poor prognosis and response to CDK4/6 inhibitors in breast cancer.Breast cancer research : BCR · 2026Article
- Aurora Kinase A inhibitor alisertib failed to exert its efficacy on TNBC cells due to consequential enrichment of polyploid giant cancer cells (PGCCs).Discover oncology · 2025Article
- A Modular Biomimetic Preclinical Platform to Elucidate the Interaction Between Cancer Cells and the Bone Metastatic Niche.Journal of functional biomaterials · 2025Article
- Lesson from a metastatic male breast cancer case: CDK4/6 plus aromatase inhibitors could not exceed tamoxifen.Discover oncology · 2025Article
- CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer.Nature communications · 2025Article
- CDK4/6 Inhibitor Resistance in ER+ Breast Cancer.Advances in experimental medicine and biology · 2025Review
- Using bioinformatics and artificial intelligence to map the cyclin-dependent kinase 4/6 inhibitor biomarker landscape in breast cancer.Future oncology (London, England) · 2024Review
- Roles and mechanisms of aberrant alternative splicing in melanoma - implications for targeted therapy and immunotherapy resistance.Cancer cell international · 2024Review
- Development of a long term, ex vivo, patient-derived explant model of endometrial cancer.PloS one · 2024Article
- Comparison of primary and passaged tumor cell cultures and their application in personalized medicine.Exploration of targeted anti-tumor therapy · 2024Review
- Identification of a targetable JAK-STAT enriched androgen receptor and androgen receptor splice variant positive triple-negative breast cancer subtype.Cell reports · 2023Article
- Upregulated PARP1 confers breast cancer resistance to CDK4/6 inhibitors via YB-1 phosphorylation.Experimental hematology & oncology · 2023Article
- The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancers · 2023Review
- Progression after First-Line Cyclin-Dependent Kinase 4/6 Inhibitor Treatment: Analysis of Molecular Mechanisms and Clinical Data.International journal of molecular sciences · 2023Review
- The Therapeutic Potential of CDK4/6 Inhibitors, Novel Cancer Drugs, in Kidney Diseases.International journal of molecular sciences · 2023Review
- Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines.International journal of molecular sciences · 2023Article
74 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
Abstract
To model the heterogeneity of breast cancer as observed in the clinic, we employed an ex vivo model of breast tumor tissue. This methodology maintained the histological integrity of the tumor tissue in unselected breast cancers, and importantly, the explants retained key molecular markers that are currently used to guide breast cancer treatment (e.g., ER and Her2 status). The primary tumors displayed the expected wide range of positivity for the proliferation marker Ki67, and a strong positive correlation between the Ki67 indices of the primary and corresponding explanted tumor tissues was observed. Collectively, these findings indicate that multiple facets of tumor pathophysiology are recapitulated in this ex vivo model. To interrogate the potential of this preclinical model to inform determinants of therapeutic response, we investigated the cytostatic response to the CDK4/6 inhibitor, PD-0332991. This inhibitor was highly effective at suppressing proliferation in approximately 85% of cases, irrespective of ER or HER2 status. However, 15% of cases were completely resistant to PD-0332991. Marker analyses in both the primary tumor tissue and the corresponding explant revealed that cases resistant to CDK4/6 inhibition lacked the RB-tumor suppressor. These studies provide important insights into the spectrum of breast tumors that could be treated with CDK4/6 inhibitors, and defines functional determinants of response analogous to those identified through neoadjuvant studies.
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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.