ArticleNPJ precision oncology2025
IL-6 predicts CDK4/6 inhibitor resistance, identifying STAT3 as a target in HR + /HER2-negative metastatic breast cancer.
Article in NPJ precision oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed.
- The peripheral immune landscape of human breast cancer.Oncoimmunology · 2026Review
- The immunology of human breast cancer.Nature reviews. Immunology · 2026Review
- Review
- CDK4/6 Inhibitor-Induced Senescence in Cancer: Mechanisms and Therapeutic Implications.Cancers · 2026Review
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Real-world study of treatment patterns and outcomes in patients with HR+ breast cancer after progression on CDK4/6 inhibitor therapy.Lancet regional health. Americas · 2026Article
- CDK4/6 Inhibition Induces CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Breast Cancer and Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2026Review
- CDK4/6 inhibition uncovers subtype-specific vulnerabilities and immune-related responses in esophageal squamous cell carcinoma.Cell death & disease · 2026Article
- Article
- Multidimensional single-cell analysis of the molecular characteristics and functional pathways of Regulatory T cells in the microenvironment of HR+ breast cancer.Discover oncology · 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
- CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction.Nature communications · 2026Article
- Case Report: Synergistic potential of RANKL and ACLY inhibition in a breast cancer patient with acquired resistance to CDK4/6 inhibitors.Frontiers in oncology · 2026Article
- Emerging hallmarks and the rise of complexities and heterogeneity of tumor.Biochemistry and biophysics reports · 2025Review
- Cytokine signaling and resistance to CDK4/6 inhibitors in HRNPJ precision oncology · 2025Article
Corrections and comments
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Authors and funding
24 authors.
Funding
Abstract
Resistance to CDK4/6 inhibitors (CDK4/6i) is a major challenge in treating hormone receptor-positive, HER2-negative metastatic breast cancer. This study aimed to identify a biomarker predictive of resistance that could also serve as a therapeutic target. Circulating IL-6 levels in 166 patients significantly increased at progression, making IL-6 a non-invasive biomarker to predict CDK4/6i resistance. Knockdown of IL-6 re-sensitized resistant cells to palbociclib and endocrine therapy, underscoring IL-6's critical role in maintaining resistance. Patient-derived xenograft models from patients who progressed within 3 months versus ≥6 months of palbociclib therapy revealed distinct transcriptomic profiles, with later progressors exhibiting IL-6/STAT3 activation, epithelial-to-mesenchymal transition, and immune evasion signatures. Treatment with TTI-101, a STAT3 inhibitor, significantly reduced tumor growth and improved survival in these models, providing preclinical validation for targeting the IL-6/STAT3 axis. These findings support using IL-6 to guide personalized treatment and combining STAT3 inhibitors with CDK4/6i as a transformative strategy to overcome resistance.
Identifiers
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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.