ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Activation of the IFN Signaling Pathway is Associated with Resistance to CDK4/6 Inhibitors and Immune Checkpoint Activation in ER-Positive Breast Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. 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 58 papers.
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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.
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Who cites it
58 citing papers in PubMed, 91 citations in OpenAlex.
- Biomarkers of response to neoadjuvant palbociclib plus anastrozole in endocrine-resistant estrogen receptor-positive/HER2-negative breast cancer: a phase 2 trial.Nature communications · 2026Trial
- Palbociclib and endocrine therapy diminish adaptive anti-tumor immunity in early breast cancer: The NeoRHEA phase 2 study.Nature communications · 2025Trial
- Biomarkers of Response and Resistance to Palbociclib Plus Letrozole in Patients With ERClinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Targeting SUV39H2 exon skipping reverses resistance to CDK4/6 inhibitors via transcriptional activation of p21.Science advances · 2026Article
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Article
- Alternative Splicing in Cyclin-Dependent Kinase 4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer.Drug development research · 2026Review
- Bioinformatic Analysis to Identify Biomarker Candidates of Complex Karyotype Soft Tissue Sarcomas withBiomolecules & therapeutics · 2026Article
- JAK/STAT1-interferon-ISGylation networks in breast cancer resistance to inhibitors of FOXM1 and CDK4/6.NPJ breast cancer · 2026Article
- Isoform-specific single-cell perturb-seq reveals distinct functions of alternative promoters in drug response.Nucleic acids research · 2026Article
- Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.Breast cancer (Dove Medical Press) · 2026Review
- The Dual Effects of CDK4/6 Inhibitors on Tumor Immunity.Cancers · 2025Review
- Next-generation sequencing methodologies to identify patients for targeted therapy: focus on HR+/HER2- metastatic breast cancer.Pathologica · 2025Review
- IL-17A-secreting γδ T cells promote resistance to CDK4/CDK6 inhibitors in HRNature cancer · 2025Article
- The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- Single-cell transcriptomics reveals biomarker heterogeneity linked to CDK4/6 Inhibitor resistance in breast cancer cell lines.NPJ breast cancer · 2025Article
- Review
- Genomic Characteristics Related to Histology-Based Immune Features in Breast Cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- Molecular Mechanisms and Therapeutic Strategies to Overcome Resistance to Endocrine Therapy and CDK4/6 Inhibitors in Advanced ER+/HER2- Breast Cancer.International journal of molecular sciences · 2025Review
- Immunomodulation on tumor immune microenvironment in acquired targeted therapy resistance and implication for immunotherapy resistance.Translational oncology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
30 authors at 7 institutions in 2 countries.
Funding
Abstract
purposeCyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor-positive (ER EXPERIMENTAL
designParental breast cancer cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation-resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes.
resultsParental and EndoR breast cancer lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high IFN signaling and reduced CDK4/6i sensitivity; thus an "IFN-related palbociclib-resistance Signature" (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1 signaling compared with their short-term treated or untreated counterparts. In primary ER
conclusionsAberrant IFN signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i.
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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.