ArticleNature communications2025
Real-world clinical multi-omics analyses reveal bifurcation of ER-independent and ER-dependent drug resistance to CDK4/6 inhibitors.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Evolving First-Line Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer: CDK4/6 Inhibition, Biomarker-Guided Strategies and Emerging Therapeutic Paradigms.Current oncology (Toronto, Ont.) · 2026Review
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- ESR1 mutations and CDK4/6 inhibitor choice shape clonal selection and adaptive cell states during acquired resistance.Genome medicine · 2026Article
- Multi-omics and artificial intelligence for precision drug discovery and potential clinical applications.Signal transduction and targeted therapy · 2026Review
- Review
- Real-world second- and third-line progression-free survival after progression on first-line CDK4/6 inhibitors in HR+/HER2- metastatic breast cancer by PAM50 intrinsic subtype: the SOLTI-1801 CDK-PREDICT study.Breast cancer research and treatment · 2026Observational
- Real-World Genomic Landscape of Korean Gastric Cancer: Integrating Biomarker Associations and Clinical Outcomes in Metastatic Gastric Cancer.JCO precision oncology · 2026Article
- Anwei decoction alleviates chronic atrophic gastritis by modulating the gut microbiota-metabolite axis andWorld journal of gastroenterology · 2026Article
- Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026Review
- Rectal metastasis in a patient with long-term breast cancer: a rare case report with literature review.Frontiers in oncology · 2026Article
- Comparative Analysis of Pathology Foundation Models for Automated Detection of Tertiary Lymphoid Structures in Hematoxylin-and-Eosin-Stained Digital Pathology Images.Computational and structural biotechnology journal · 2026Article
- Advances in Cutaneous Melanoma Therapy: The Emerging Role of CDK4/6 Inhibitors.Pharmacological research · 2025Review
- Navigating Treatment Sequencing in Advanced HR+/HER2- Breast Cancer After CDK4/6 Inhibitors: Biomarker-Driven Strategies and Emerging Therapies.International journal of molecular sciences · 2025Review
- Artificial Intelligence and Multi-Omics in Pharmacogenomics: A New Era of Precision Medicine.Mayo Clinic proceedings. Digital health · 2025Review
- Extracellular Vesicle-Derived miRNAs in Ischemic Stroke: Roles in Neuroprotection, Tissue Regeneration, and Biomarker Potential.Cellular and molecular neurobiology · 2025Review
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To better understand drug resistance mechanisms to CDK4/6 inhibitors and inform precision medicine, we analyze real-world multi-omics data from 400 HR+/HER2- metastatic breast cancer patients treated with CDK4/6 inhibitors plus endocrine therapies, including 200 pre-treatment and 227 post-progression samples. The prevalences of ESR1 and RB1 alterations significantly increase in post-progression samples. Integrative clustering analysis identifies three subgroups harboring different resistance mechanisms: ER driven, ER co-driven and ER independent. The ER independent subgroup, growing from 5% pre-treatment to 21% post-progression, is characterized by down-regulated estrogen signaling and enrichment of resistance markers including TP53 mutations, CCNE1 over-expression and Her2/Basal subtypes. Trajectory inference analyses identify a pseudotime variable strongly correlated with ER independence and disease progression; and revealed bifurcated evolutionary trajectories for ER-independent vs. ER-dependent drug resistance mechanisms. Machine learning models predict therapeutic dependency on ESR1 and CDK4 among ER-dependent tumors and CDK2 dependency among ER-independent tumors, confirmed by experimental validation.
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