ArticleNature communications2022
High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER
Article in Nature communications, 2022. 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 79 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 115 citations in OpenAlex.
- CDK4/6 Inhibition in the Management of Metastatic HR+/HER2+ Breast Cancer: Systematic Review and Meta-analysis.Targeted oncology · 2026Pooled it
- CDK4/6 inhibitors as conditional immune-priming agents in breast cancer: therapeutic windows, sequencing strategies, and rational combinations with immunotherapy, radiotherapy, and antibody-drug conjugates.Frontiers in immunology · 2026Pooled it
- A pilot translational study of neoadjuvant fulvestrant plus abemaciclib in women with advanced low-grade serous carcinoma.Nature communications · 2026Trial
- CDK4/6 Inhibitors in Breast Cancer Therapy: Mechanisms, Resistance, and Emerging Opportunities.Targeted oncology · 2026Review
- Article
- Alternative Splicing in Cyclin-Dependent Kinase 4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer.Drug development research · 2026Review
- Timing and Patterns of Relapse-Related Events Following Adjuvant CDK4/6 Inhibitors Combined With Endocrine Therapy in Patients With HR-Positive, HER2-Negative Early Breast Cancer.Cancer medicine · 2026Article
- Navigating first- and second-line treatment options in hormone receptor-positive HER2-negative advanced breast cancer.The oncologist · 2026Review
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Integration of gene expression profiling and mutation analysis via RNA sequencing: transitioning the 95-gene classifier to a next-generation platform in early-stage HR+/HER2- breast cancer.Breast cancer (Tokyo, Japan) · 2026Article
- CDK4/6 Inhibitors for Breast Cancer Therapy-A Review of Clinical Trials, Structural and Computational Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Altered Estrogen Receptor Signaling Pathway in BRCA2-Deficient Estrogen Receptor-Positive/HER2-Negative Breast Cancer.Cancer reports (Hoboken, N.J.) · 2026Article
- Rb expression in metastatic ER-positive breast cancer: implications for precision oncology.Breast cancer research and treatment · 2026Article
- TGFβ signaling promotes cell cycle progression and resistance to the CDK4/6 inhibitor palbociclib through SOX4 transcriptional modulation in breast cancer cells.Cell death & disease · 2026Article
- Precision targeting ofTranslational cancer research · 2026Article
- Genome-wide screenings identify BAP1 as a synthetic-lethality target with CDK4/6 inhibitors.Science advances · 2026Article
- Therapeutic advances in HR+/HER2- advanced breast cancer after failure of CDK4/6 inhibitor therapy.Frontiers in oncology · 2026Review
- Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.Breast cancer (Dove Medical Press) · 2026Review
- Biomarkers of primary and secondary resistance to cyclin dependent kinases 4 and 6 inhibitors in metastatic estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer: a narrative review.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Review
- Lipid metabolism reprogramming: key mechanism of breast cancer endocrine therapy resistance.Frontiers in oncology · 2026Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
38 authors at 16 institutions in 5 countries.
Funding
Abstract
CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n = 89). We also identified heterozygous RB1 loss as biomarker of acquired resistance and poor clinical outcome. Combination of the CDK4/6 inhibitor ribociclib with the PI3K inhibitor alpelisib showed antitumor activity in estrogen receptor-positive non-basal-like breast cancer patient-derived xenografts, independently of PIK3CA, ESR1 or RB1 mutation, also in drug de-escalation experiments or omitting endocrine therapy. Our results offer insights into predicting primary/acquired resistance to CDK4/6 inhibitors and post-progression therapeutic strategies.
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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.