ArticleNPJ precision oncology2022
Co-targeting CDK2 and CDK4/6 overcomes resistance to aromatase and CDK4/6 inhibitors in ER+ breast cancer.
Article in NPJ precision oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Disentangling the inverse relationship between cancer and Alzheimer's or Parkinson's disease: A systematic review on Mendelian randomization studies.Neurobiology of disease · 2025Pooled it
- Transcriptional Heterogeneity in Dedifferentiated Liposarcoma Reveals Distinct Cell-Cycle Subtypes.Annals of surgical oncology · 2026Article
- CDK8/19 inhibition prevents adaptive resistance to CDK4/6 inhibitors in vitro and in vivo.Cell reports. Medicine · 2026Article
- Adaptive mechanisms and emerging cancer therapeutics for CDK2 inhibitors.Nature chemical biology · 2026Review
- WITHDRAWN: From CDK4/6 to CDK2 and KAT: Evolving therapeutic approaches in HR+/HER2- breast cancer.Breast (Edinburgh, Scotland) · 2026Article
- Molecular modulators of cyclin-dependent kinase 4/6 inhibitor response in experimental glioma identified through genome-wide CRISPR-Cas9 screening.Neuro-oncology · 2026Article
- Non-Genetic Mechanisms of Fractional Resistance to Abemaciclib in Dedifferentiated Liposarcoma.bioRxiv : the preprint server for biology · 2026Article
- TP53 mutation is associated with shorter treatment duration with CDK4/6 inhibitors, but not with immune checkpoint inhibitors, in ER-positive/HER2-negative breast cancer: real-world perspective.Breast cancer research : BCR · 2026Article
- Cyclin E modulates vulnerability to CDC7 kinase inhibition.Oncogenesis · 2026Article
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- Emerging Strategies to Inhibit the G1/S Transition for Cancer Therapy.Cancer research · 2026Review
- Tumor cell cycle regulation: integrated perspective of stage characteristics, regulatory networks, and signaling pathway intervention strategies.Molecular biomedicine · 2026Review
- Cancer-associated adipocytes confer CDK4/6 inhibitor resistance in ER+ breast cancer through an IL-6/STAT3/SREBF2 axis coupled with cholesterol metabolism and cell cycle reprogramming.International journal of biological sciences · 2026Article
- Article
- CDK2 inhibition enhances CDK4/6 inhibitor antitumor activity in comprehensive breast cancer PDX model screen.NPJ breast cancer · 2025Article
- Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Genomics-led approach to drug testing in models of undifferentiated pleomorphic sarcoma.Molecular oncology · 2025Article
- Therapeutic benefits of maintaining CDK4/6 inhibitors and incorporating CDK2 inhibitors beyond progression in breast cancer.bioRxiv : the preprint server for biology · 2025Article
- Targeting CDK2 for cancer therapy.Cell reports · 2025Review
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Resistance to aromatase inhibitor (AI) treatment and combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) are crucial clinical challenges in treating estrogen receptor-positive (ER+) breast cancer. Understanding the resistance mechanisms and identifying reliable predictive biomarkers and novel treatment combinations to overcome resistance are urgently needed. Herein, we show that upregulation of CDK6, p-CDK2, and/or cyclin E1 is associated with adaptation and resistance to AI-monotherapy and combined CDK4/6i and ET in ER+ advanced breast cancer. Importantly, co-targeting CDK2 and CDK4/6 with ET synergistically impairs cellular growth, induces cell cycle arrest and apoptosis, and delays progression in AI-resistant and combined CDK4/6i and fulvestrant-resistant cell models and in an AI-resistant autocrine breast tumor in a postmenopausal xenograft model. Analysis of CDK6, p-CDK2, and/or cyclin E1 expression as a combined biomarker in metastatic lesions of ER+ advanced breast cancer patients treated with AI-monotherapy or combined CDK4/6i and ET revealed a correlation between high biomarker expression and shorter progression-free survival (PFS), and the biomarker combination was an independent prognostic factor in both patients cohorts. Our study supports the clinical development of therapeutic strategies co-targeting ER, CDK4/6 and CDK2 following progression on AI-monotherapy or combined CDK4/6i and ET to improve survival of patients exhibiting high tumor levels of CDK6, p-CDK2, and/or cyclin E1.
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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.