ArticleCancer cell2016
Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors.
Article in Cancer cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02947685 (A Randomized, Open Label, Phase III Trial to Evaluate the Efficacy and Safety of Palbociclib + Anti-HER2 Therapy + Endocrine Therapy vs. Anti-HER2 Therapy + Endocrine Therapy After Induction Treatment for Hormone Receptor Positive), which is not on this map. Cited by 279 papers, 3 of them syntheses 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.
A Randomized, Open Label, Phase III Trial to Evaluate the Efficacy and Safety of Palbociclib + Anti-HER2 Therapy + Endocrine Therapy vs. Anti-HER2 Therapy + Endocrine Therapy After Induction Treatment for Hormone Receptor Positive (HR+)/HER2-Positive Metastatic Breast Cancer
Who cites it
279 citing papers in PubMed, 3 syntheses or guidelines pooled it, 478 citations in OpenAlex.
- Dose reduction and discontinuation due to the combination of CDK4/6 inhibitors and endocrine drugs: a systematic review and meta-analysis.European journal of clinical pharmacology · 2024Pooled it
- Efficacy and Safety of Anti-HER2 Agents in Combination With Chemotherapy for Metastatic HER2-Positive Breast Cancer Patient: A Network Meta-Analysis.Frontiers in oncology · 2021Pooled it
- LncRNA SNHG15: A new budding star in human cancers.Cell proliferation · 2020Pooled it
- Efficacy and safety of neoadjuvant treatment of trastuzumab and pyrotinib plus dalpiciclib in HR-negative/HER2-positive breast cancer: an exploratory, open-label phase II study.International journal of surgery (London, England) · 2026Trial
- Tumor microenvironment delineates differential responders to trastuzumab emtansine in HER2-positive metastatic breast cancer patients previously treated with pyrotinib: an exploratory biomarker analysis of a phase II study (NJMU-BC02).Signal transduction and targeted therapy · 2025Trial
- Dalpiciclib combined with pyrotinib and endocrine therapy in women with ER-positive, HER2-positive advanced breast cancer: A prospective, multicenter, single-arm, phase 2 trial.PLoS medicine · 2025Trial
- Clinical characterization, prognostic, and predictive values of HER2-low in patients with early breast cancer in the PALLAS trial (ABCSG-42/AFT-05/BIG-14-13/PrE0109).Breast cancer research : BCR · 2024Trial
- Overall Survival and Exploratory Biomarker Analyses of Abemaciclib plus Trastuzumab with or without Fulvestrant versus Trastuzumab plus Chemotherapy in HR+, HER2+ Metastatic Breast Cancer Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Dalpiciclib and pyrotinib in women with HER2-positive advanced breast cancer: a single-arm phase II trial.Nature communications · 2023Trial
- A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer.Nature communications · 2022Trial
- Modulation of the Estrogen/erbB2 Receptors Cross-talk by CDK4/6 Inhibition Triggers Sustained Senescence in Estrogen Receptor- and ErbB2-positive Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Right-sizing treatment for HER2-positive breast cancer: evolving algorithms across the disease continuum.Nature reviews. Clinical oncology · 2026Review
- Loss of Erbin in tubular epithelial cells sensitizes mice to acute kidney injury and aggravates renal fibrosis.The EMBO journal · 2026Article
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- Article
- 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
- GATESynergy: Integrating Molecular Global-Local Aggregator and Hierarchical Gene-Gated Encoder for Drug Synergy Prediction.Interdisciplinary sciences, computational life sciences · 2026Article
- MKRN2-Mediated Degradation of IGF2BP3 Suppresses MYC and Enhances CDK4/6 Inhibitor Sensitivity in Bladder Cancer.Cancers · 2026Article
- CDK4/6 inhibition enhances CAR-T cell therapy in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
219 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
Using transgenic mouse models, cell line-based functional studies, and clinical specimens, we show that cyclin D1/CDK4 mediate resistance to targeted therapy for HER2-positive breast cancer. This is overcome using CDK4/6 inhibitors. Inhibition of CDK4/6 not only suppresses Rb phosphorylation, but also reduces TSC2 phosphorylation and thus partially attenuates mTORC1 activity. This relieves feedback inhibition of upstream EGFR family kinases, resensitizing tumors to EGFR/HER2 blockade. Consequently, dual inhibition of EGFR/HER2 and CDK4/6 invokes a more potent suppression of TSC2 phosphorylation and hence mTORC1/S6K/S6RP activity. The suppression of both Rb and S6RP enhances G1 arrest and a phenotype resembling cellular senescence. In vivo, CDK4/6 inhibitors sensitize patient-derived xenograft tumors to HER2-targeted therapies and delay tumor recurrence in a transgenic model of HER2-positive breast cancer.
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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.