ArticleGenome medicine2023
Longitudinal multi-omics study of palbociclib resistance in HR-positive/HER2-negative metastatic breast cancer.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03401359 (Prospective Longitudinal Biomarker Study of Acquired Resistance and Immune Response to Palbociclib in Breast Cancer), which is not on this map. Cited by 42 papers.
What it found
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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.
Prospective Longitudinal Biomarker Study of Acquired Resistance and Immune Response to Palbociclib in Breast Cancer
Who cites it
42 citing papers in PubMed, 53 citations in OpenAlex.
- Continuous versus Standard Palbociclib Treatment and Molecular Profiling of Solid Tissues and Liquid Biopsies in the CCTG MA.38 Trial in Advanced Breast Cancer.Cancer research communications · 2025Trial
- Trial
- Tracking CDK1 Dynamics With a Novel Biosensor Mouse and Clinical Cohorts to Predict CDK4/6 Inhibitor Sensitivity in ER+ Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LC-MS/MS-based clinical value exploration of the methionine cycle in luminal breast cancer.Oncology letters · 2026Article
- Multi-Omics-Driven Insights into Cancer Biology and Therapeutic Targeting.AAPS PharmSciTech · 2026Review
- CRISPR activation screens identify oncogenic lncRNAs that are susceptible to CDK4/6 inhibitor treatment.Nature communications · 2026Article
- BRCA1/2, PALB2 mutations and first-line CDK4/6 inhibitor efficacy in HR+ metastatic breast cancer.Breast (Edinburgh, Scotland) · 2026Article
- Machine Learning-Based Analysis of Large-Scale Transcriptomic Data Identifies Core Genes Associated with Multi-Drug Resistance.International journal of molecular sciences · 2026Article
- LEM4 interacts with β-catenin and promotes β-catenin-dependent transcription activity to confers ribociclib resistance in breast cancer cells.Scientific reports · 2025Article
- Circulating tumor cells in breast cancer bone metastasis: mechanisms, clinical relevance, and future directions.Cell death discovery · 2025Review
- Breast Cancer Progression and Its Theranostic Management via Folate-Directed Targeting of Glycoprotein Receptor.Medical sciences (Basel, Switzerland) · 2025Review
- Contrasting roles of KMT2C and KMT2D in breast cancer.Scientific reports · 2025Article
- Multi-omics analysis reveals the prognostic value and immunomodulatory role of CTSW in breast cancer.Discover oncology · 2025Article
- Flexynesis: A deep learning toolkit for bulk multi-omics data integration for precision oncology and beyond.Nature communications · 2025Article
- BLID is a drug-responsive target of FOXO3a and multi-omics analysis reveals survival mechanisms and therapeutic vulnerabilities in BLID-deficient breast cancer cells.Oncology letters · 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
- Analyzing the Blueprint: Exploring the Molecular Profile of Metastasis and Therapeutic Resistance.International journal of molecular sciences · 2025Review
- Prevalence of germlineThe Lancet regional health. Western Pacific · 2025Article
- Establishment and characterization of 24 breast cancer cell lines and 3 breast cancer organoids reveals molecular heterogeneity and drug response variability in malignant pleural effusion-derived models.Breast cancer research : BCR · 2025Article
- Article
Corrections and comments
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Authors and funding
34 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCyclin-dependent kinase 4/6 inhibitor (CDK4/6) therapy plus endocrine therapy (ET) is an effective treatment for patients with hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer (HR+/HER2- MBC); however, resistance is common and poorly understood. A comprehensive genomic and transcriptomic analysis of pretreatment and post-treatment tumors from patients receiving palbociclib plus ET was performed to delineate molecular mechanisms of drug resistance.
methodsTissue was collected from 89 patients with HR+/HER2- MBC, including those with recurrent and/or metastatic disease, receiving palbociclib plus an aromatase inhibitor or fulvestrant at Samsung Medical Center and Seoul National University Hospital from 2017 to 2020. Tumor biopsy and blood samples obtained at pretreatment, on-treatment (6 weeks and/or 12 weeks), and post-progression underwent RNA sequencing and whole-exome sequencing. Cox regression analysis was performed to identify the clinical and genomic variables associated with progression-free survival.
resultsNovel markers associated with poor prognosis, including genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four prognostic clusters with distinct molecular features were identified. Tumors with TP53 mutations co-occurring with a unique HRD-high cluster responded poorly to palbociclib plus ET. Comparisons of paired pre- and post-treatment samples revealed that tumors became enriched in APOBEC mutation signatures, and many switched to aggressive molecular subtypes with estrogen-independent characteristics. We identified frequent genomic alterations upon disease progression in RB1, ESR1, PTEN, and KMT2C.
conclusionsWe identified novel molecular features associated with poor prognosis and molecular mechanisms that could be targeted to overcome resistance to CKD4/6 plus ET.
trial registrationClinicalTrials.gov, NCT03401359. The trial was posted on 18 January 2018 and registered prospectively.
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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.