ArticleCancer cell2024
Long-term breast cancer response to CDK4/6 inhibition defined by TP53-mediated geroconversion.
Article in Cancer cell, 2024. 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 44 papers.
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
44 citing papers in PubMed.
- Trial
- Novel CDK2/4/6 inhibitor culmerciclib (TQB3616) plus fulvestrant in previously treated, HR-positive, HER2-negative advanced breast cancer: a randomized, double-blind, phase 3 trial.Signal transduction and targeted therapy · 2025Trial
- Cyclin E1 Expression Predicts Poorer Outcome in HER2-positive Breast Cancer with Residual Disease after Neoadjuvant Chemotherapy.Annals of surgical oncology · 2026Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Integrated multi-omics, machine learning, network toxicology, and molecular docking reveal potential mechanisms underlying methyl 4-hydroxybenzoate-associated breast cancer.Molecular diversity · 2026Article
- CDK4/6 Inhibitor-Induced Senescence in Cancer: Mechanisms and Therapeutic Implications.Cancers · 2026Review
- Divergent neuropsychiatric and systemic toxicity profiles of abemaciclib and palbociclib: a triangulation study integrating pharmacovigilance, genetic epidemiology, and multi-omics profiling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Comparative analysis of distinct genomic landscapes in young-onset gBRCA1/2 breast cancer.JCI insight · 2026Article
- SERENA-6 interpretation and clinical implications: intercepting endocrine resistance in metastatic breast cancer.NPJ breast cancer · 2026Article
- Beyond CDK4/6 Inhibition: Current Strategies in Hormone Receptor-Positive Metastatic Breast Cancer.Current treatment options in oncology · 2026Review
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- Homologous recombination deficiency and hemizygosity drive resistance in breast cancer.Nature · 2026Article
- Targeting a super-enhancer induced aldehyde dehydrogenase metabolic loop mitigates CDK4/6 inhibitor resistance in estrogen receptor-positive cancers.Nature communications · 2026Article
- Dalpiciclib plus chidamide in HR + /HER2-advanced breast cancer after CDK4/6 inhibitor failure: a phase Ib trial.Nature communications · 2026Article
- Targeting the p53 cancer mutants Y220C, Y220N, and Y220S with the small-molecule stabilizer rezatapopt.Cell death & disease · 2026Article
- Endocrine Therapy for Endometrial Carcinoma: Current Evidence, Resistance Mechanisms, and Biomarker-Driven Patient Selection.Current oncology (Toronto, Ont.) · 2026Review
- JAK/STAT1-interferon-ISGylation networks in breast cancer resistance to inhibitors of FOXM1 and CDK4/6.NPJ breast cancer · 2026Article
- Whole-Exome Profiling of Epstein-Barr Virus-Positive Neuroendocrine Carcinoma of the Nasopharynx.Endocrine pathology · 2026Article
- AI-driven CRISPR strategies in breast cancer: Organoid modeling, adaptive editing, and precision delivery.Iranian journal of basic medical sciences · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
28 authors.
Funding
Abstract
Inhibition of CDK4/6 kinases has led to improved outcomes in breast cancer. Nevertheless, only a minority of patients experience long-term disease control. Using a large, clinically annotated cohort of patients with metastatic hormone receptor-positive (HR+) breast cancer, we identify TP53 loss (27.6%) and MDM2 amplification (6.4%) to be associated with lack of long-term disease control. Human breast cancer models reveal that p53 loss does not alter CDK4/6 activity or G1 blockade but instead promotes drug-insensitive p130 phosphorylation by CDK2. The persistence of phospho-p130 prevents DREAM complex assembly, enabling cell-cycle re-entry and tumor progression. Inhibitors of CDK2 can overcome p53 loss, leading to geroconversion and manifestation of senescence phenotypes. Complete inhibition of both CDK4/6 and CDK2 kinases appears to be necessary to facilitate long-term response across genomically diverse HR+ breast cancers.
Indexed as
Identifiers
What Socratic holds
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.