ArticleNature communications2021
Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer.
Article in Nature communications, 2021. 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 60 papers, 1 of them a synthesis 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
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Efficacy of CDK4/6 inhibitors combined with endocrine therapy in HR+/HER2- breast cancer: an umbrella review.Journal of cancer research and clinical oncology · 2024Pooled it
- Trial
- Targeting casein kinase 1α-mediated FADD phosphorylation restores sensitivity in select CDK4/6 inhibitor-resistant breast cancer models.The Journal of clinical investigation · 2026Article
- Article
- Article
- Targeting Estrogen Receptor for Breast Cancer.Current issues in molecular biology · 2026Review
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Endocrine therapy reprogramming of breast cancer facilitates metastatic escape via upregulation of P-Rex1/Rac1 signalling.Nature communications · 2026Article
- Review
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- Loss of FAT1 drives cyclophosphamide resistance in breast cancer via the Wnt/β-Catenin pathway.International journal of biological sciences · 2026Article
- Clinical Efficacy and Security Analysis of CDK4/6 Inhibitors Combined with ET in Patients with HRCancer management and research · 2026Article
- Real-World Predictors of Survival in CDK4/6 Inhibitor-Treated Metastatic Breast Cancer: The Significance of ER Expression Level and Treatment Naivety.Current oncology (Toronto, Ont.) · 2025Article
- JNK pathway suppression mediates insensitivity to combination endocrine therapy and CDK4/6 inhibition in ER+ breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Emerging Mechanisms of Therapy Resistance in Metastatic ER+ Breast Cancer.Endocrinology · 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
- SHMT inhibitor synergizes with 5-Fu to suppress gastric cancer via cell cycle arrest and chemoresistance alleviation.NPJ precision oncology · 2025Article
- Stabilization of RUNX1 Induced by O-GlcNAcylation Promotes PDGF-BB-Mediated Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancer research · 2025Article
- Review
- Mechanisms of breast cancer metastasis: the role of extracellular matrix.Molecular and cellular biochemistry · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy have shown impressive efficacy in estrogen receptor-positive advanced breast cancer. However, most patients will eventually experience disease progression on this combination, underscoring the need for effective subsequent treatments or better initial therapies. Here, we show that triple inhibition with fulvestrant, CDK4/6i and AKT inhibitor (AKTi) durably impairs growth of breast cancer cells, prevents progression and reduces metastasis of tumor xenografts resistant to CDK4/6i-fulvestrant combination or fulvestrant alone. Importantly, switching from combined fulvestrant and CDK4/6i upon resistance to dual combination with AKTi and fulvestrant does not prevent tumor progression. Furthermore, triple combination with AKTi significantly inhibits growth of patient-derived xenografts resistant to combined CDK4/6i and fulvestrant. Finally, high phospho-AKT levels in metastasis of breast cancer patients treated with a combination of CDK4/6i and endocrine therapy correlates with shorter progression-free survival. Our findings support the clinical development of ER, CDK4/6 and AKT co-targeting strategies following progression on CDK4/6i and endocrine therapy combination, and in tumors exhibiting high phospho-AKT levels, which are associated with worse clinical outcome.
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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.