ArticleOncogene2010
Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 252 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.
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Who cites it
252 citing papers in PubMed, 397 citations in OpenAlex.
- Transcriptomic Predictors of Survival for Palbociclib + Endocrine Therapy Versus Capecitabine in Aromatase Inhibitor-Resistant Breast Cancer From the GEICAM/2013-02 PEARL Trial.JCO precision oncology · 2025Trial
- Phase 2 trial of palbociclib and ganitumab in patients with relapsed Ewing sarcoma.Cancer medicine · 2023Trial
- Cyclin E1 Expression and Palbociclib Efficacy in Previously Treated Hormone Receptor-Positive Metastatic Breast Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- Target and Agent Prioritization for the Children's Oncology Group-National Cancer Institute Pediatric MATCH Trial.Journal of the National Cancer Institute · 2017Trial
- Time-resolved proteomic and phosphoproteomic analysis reveals convergent and divergent biological perturbations induced by FDA-approved CDK4/6 inhibitors in hormone receptor-positive breast cancers.Acta pharmacologica Sinica · 2026Article
- Article
- Review
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Magnetic Levitation Derived Metabolomic Fingerprinting Enables Exploratory Discrimination of Breast Cancer Subtypes.bioRxiv : the preprint server for biology · 2026Article
- Nanoscale Direct-to-Biology Optimization of Cdk2 Inhibitors.Journal of medicinal chemistry · 2026Article
- Review
- Discovery of novel purine analogues against breast cancer selectively targeting CDK2: optimization, synthesis, biological evaluation and docking study.Molecular diversity · 2026Article
- Review
- Disrupting CDK9 activity suppresses triple-negative breast cancer and is enhanced by EGFR Inhibition.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Targeting Aurora A Kinase Enhance the CDK4/6 Inhibitor Sensitivity in HR+/HER2- Breast Cancer.Oncology research · 2026Article
- Progress in Heterocyclic Hybrids for Breast Cancer Therapy: Emerging Trends, Hybridization Techniques, Mechanistic Pathways and SAR Insights.Mini reviews in medicinal chemistry · 2026Review
- Biomarkers of primary and secondary resistance to cyclin dependent kinases 4 and 6 inhibitors in metastatic estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer: a narrative review.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Review
- Intrinsic RB activation induces tumoral and stromal anti-tumor responses that limit triple-negative breast cancer.NPJ breast cancer · 2025Article
- Article
- Efficacy of CDK4/6 Inhibition in colorectal cancer and the role of p16 expression in predicting drug resistance.Cellular oncology (Dordrecht, Netherlands) · 2025Article
192 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
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A hallmark of cancer is the deregulation of cell-cycle machinery, ultimately facilitating aberrant proliferation that fuels tumorigenesis and disease progression. Particularly, in breast cancers, cyclin D1 has a crucial role in the development of disease. Recently, a highly specific inhibitor of CDK4/6 activity (PD-0332991) has been developed that may have efficacy in the treatment of breast cancer. To interrogate the utility of PD-0332991 in treating breast cancers, therapeutic response was evaluated on a panel of breast cancer cell lines. These analyses showed that the chronic loss of Rb is specifically associated with evolution to a CDK4/6-independent state and, ultimately, resistance to PD-0332991. However, to interrogate the functional consequence of Rb directly, knockdown experiments were performed in models that represent immortalized mammary epithelia and multiple subtypes of breast cancer. These studies showed a highly specific role for Rb in mediating the response to CDK4/6 inhibition that was dependent on transcriptional repression manifest through E2F, and the ability to attenuate CDK2 activity. Acquired resistance to PD-03322991 was specifically associated with attenuation of CDK2 inhibitors, indicating that redundancy in CDK functions represents a determinant of therapeutic failure. Despite these caveats, in specific models, PD-0332991 was a particularly effective therapy, which induced Rb-dependent cytostasis. Combined, these findings indicate the critical importance of fully understanding cell-cycle regulatory pathways in directing the utilization of CDK inhibitors in the clinic.
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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.