ArticleGenes & cancer2014
CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models.
Article in Genes & cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 67 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- CDK4/6 Inhibition in the Management of Metastatic HR+/HER2+ Breast Cancer: Systematic Review and Meta-analysis.Targeted oncology · 2026Pooled it
- 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
- Emerging Strategies to Inhibit the G1/S Transition for Cancer Therapy.Cancer research · 2026Review
- Next Frontier in HER2+/HR+ Breast Cancer: Leveraging Cell Cycle Control with CDK4/6 Inhibitors.Journal of personalized medicine · 2026Review
- Phase I trial of neratinib plus palbociclib in advanced cancers with HER family alterations.ESMO open · 2025Article
- Efficacy and Predictability of Cyclin-Dependent Kinase 4/6 Inhibitors in HER2-Positive Breast Cancer.Cancers · 2025Review
- Targeting CDK2 and other novel cell cycle targets for breast cancer therapy.Expert opinion on therapeutic targets · 2025Review
- Long‑term progression‑free survival in HR+/HER2+ advanced breast cancer with combination therapy with a CDK4/6 inhibitor and first‑line maintenance therapy: A case report.Oncology letters · 2025Article
- Mechanistic optimization of inavolisib combined with CDK4/6 inhibitors in the treatment of PIK3CA-mutated breast tumors.Frontiers in immunology · 2025Review
- The next frontier in antibody-drug conjugates: challenges and opportunities in cancer and autoimmune therapy.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Unveiling the future of breast cancer therapy: Cutting-edge antibody-drug conjugate strategies and clinical outcomes.Breast (Edinburgh, Scotland) · 2024Review
- Hormone Receptor-Positive/HER2-Positive Breast Cancer: Hormone Therapy and Anti-HER2 Treatment: An Update on Treatment Strategies.Journal of clinical medicine · 2024Review
- The CDK4/6 inhibitor revolution - a game-changing era for breast cancer treatment.Nature reviews. Clinical oncology · 2024Review
- Safety and Efficacy of Tucatinib, Letrozole, and Palbociclib in Patients with Previously Treated HR+/HER2+ Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Recent Advances in Drug Discovery for Triple-Negative Breast Cancer Treatment.Molecules (Basel, Switzerland) · 2023Review
- CDK4/6 Inhibitor Resistance in Hormone Receptor-Positive Metastatic Breast Cancer: Translational Research, Clinical Trials, and Future Directions.International journal of molecular sciences · 2023Review
- Platform combining statistical modeling and patient-derived organoids to facilitate personalized treatment of colorectal carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Resistance to antibody-drug conjugates in breast cancer: mechanisms and solutions.Cancer communications (London, England) · 2023Review
- Discovery of IHMT-337 as a potent irreversible EZH2 inhibitor targeting CDK4 transcription for malignancies.Signal transduction and targeted therapy · 2023Article
- Can Patients with HER2-Low Breast Cancer Benefit from Anti-HER2 Therapies? A Review.Breast cancer (Dove Medical Press) · 2023Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
In spite of the efficacy of Her2-targeted therapies, recurrence and progression remain a challenge for treatment of Her2 positive breast cancer. CDK4/6 controls pathway downstream of Her2, Inhibition of these kinases could represent an important therapeutic approach to augment the effectiveness of standard therapies. In models of acquired resistance to Her2-targeted therapies, Cyclin D1 was inappropriately activated and CDK4/6 inhibition was effective at blocking proliferation by targeting this common pathway associated with resistance. These data were recapitulated in Her2 positive xenografts. Furthermore, in a series of 35 primary breast tumor explants, treatment with PD-0332991 resulted in a greater than 4-fold suppression of the Ki67. The effects of CDK4/6 inhibition were dependent on an intact RB-pathway, and consonantly, loss of RB and high-levels of p16 were associated with resistance to CDK4/6 inhibition. Combination studies illustrated that CDK4/6 inhibition is cooperative with multiple Her2-targeted agents and provides a complementary mechanism of action to T-DM1 to efficiently suppresses the proliferation of residual Her2-positive tumor cell populations that survive T-DM1. Together, these data indicate CDK4/6 is a viable therapeutic target that functions downstream of Her2, and tissue based markers are available to direct rational utilization of CDK4/6 inhibitors in combination with Her2-targeted agents.
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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.