ArticleCancer cell2014
CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors.
Article in Cancer cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 262 papers, 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
262 citing papers in PubMed, 2 syntheses or guidelines pooled it, 432 citations in OpenAlex.
- CDK4/6 inhibitors versus PI3K/AKT/mTOR inhibitors in women with hormone receptor-positive, HER2-negative metastatic breast cancer: An updated systematic review and network meta-analysis of 28 randomized controlled trials.Frontiers in oncology · 2022Pooled it
- Pooled it
- Trial
- Letrozole, abemaciclib and metformin in endometrial cancer: a non-randomized phase 2 trial.Nature communications · 2025Trial
- Overall Survival with Inavolisib inThe New England journal of medicine · 2025Trial
- FDA Approval Summary: Alpelisib Plus Fulvestrant for Patients with HR-positive, HER2-negative, PIK3CA-mutated, Advanced or Metastatic Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Efficacy of Palbociclib Combinations in Hormone Receptor-Positive Metastatic Breast Cancer Patients After Prior Everolimus Treatment.Clinical breast cancer · 2018Trial
- Phase II trial of palbociclib in patients with metastatic urothelial cancer after failure of first-line chemotherapy.British journal of cancer · 2018Trial
- Targeting casein kinase 1α-mediated FADD phosphorylation restores sensitivity in select CDK4/6 inhibitor-resistant breast cancer models.The Journal of clinical investigation · 2026Article
- Combined inhibition of CDK4/6 and PI3K pathways exhibit highly synergistic activity and translational potential in Ewing sarcoma.Translational oncology · 2026Article
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Capivasertib as a Therapeutic Agent for Breast Cancer: Targeting AKT to Overcome Endocrine Resistance.Journal of clinical medicine · 2026Review
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- Multidimensional tumor heterogeneity and its role in therapeutic resistance.Frontiers in immunology · 2026Review
- CDK4/6 Inhibitors in Breast Cancer-Who Should Receive Them?International journal of molecular sciences · 2025Review
- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- Functional Analysis of the PI3K/AKT/mTOR Pathway Inhibitor, Gedatolisib, Plus Fulvestrant with and Without Palbociclib in Breast Cancer Models.International journal of molecular sciences · 2025Article
- Review
- Molecular Mechanisms and Therapeutic Strategies to Overcome Resistance to Endocrine Therapy and CDK4/6 Inhibitors in Advanced ER+/HER2- Breast Cancer.International journal of molecular sciences · 2025Review
- Dual Inhibition of CDK4/6 and CDK7 Suppresses Triple-Negative Breast Cancer Progression via Epigenetic Modulation of SREBP1-Regulated Cholesterol Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
202 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Activation of the phosphoinositide 3-kinase (PI3K) pathway occurs frequently in breast cancer. However, clinical results of single-agent PI3K inhibitors have been modest to date. A combinatorial drug screen on multiple PIK3CA mutant cancers with decreased sensitivity to PI3K inhibitors revealed that combined CDK 4/6-PI3K inhibition synergistically reduces cell viability. Laboratory studies revealed that sensitive cancers suppress RB phosphorylation upon treatment with single-agent PI3K inhibitors but cancers with reduced sensitivity fail to do so. Similarly, patients' tumors that responded to the PI3K inhibitor BYL719 demonstrated suppression of pRB, while nonresponding tumors showed sustained or increased levels of pRB. Importantly, the combination of PI3K and CDK 4/6 inhibitors overcomes intrinsic and adaptive resistance leading to tumor regressions in PIK3CA mutant xenografts.
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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 Socratic graph.