ArticleNature communications2019
Single-cell profiling guided combinatorial immunotherapy for fast-evolving CDK4/6 inhibitor-resistant HER2-positive breast cancer.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
- Targeting receptor tyrosine kinases: from molecular mechanisms to clinical therapeutics.Signal transduction and targeted therapy · 2026Review
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Iron diminishes immunosuppressive macrophages and enhances anti-PD-1 immunotherapy in breast cancer models.Journal of experimental & clinical cancer research : CR · 2026Article
- Molecular and cellular composition changes after neoadjuvant letrozole and palbociclib in early luminal breast cancer.Cell reports. Medicine · 2026Article
- Cyclin-dependent kinase 4 and 6 inhibitors and the breast cancer immune ecosystem: immune remodeling, resistance, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- The Dual Effects of CDK4/6 Inhibitors on Tumor Immunity.Cancers · 2025Review
- Modelling the metastatic immune microenvironment in triple-negative breast cancer.Breast cancer research : BCR · 2025Article
- Targeting the CCL5/CCR5 axis in tumor-stromal crosstalk to overcome cisplatin resistance in neuroendocrine prostate cancer.Journal of experimental & clinical cancer research : CR · 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
- Immunomodulation on tumor immune microenvironment in acquired targeted therapy resistance and implication for immunotherapy resistance.Translational oncology · 2025Review
- CDK4/6 Inhibitor Resistance in ER+ Breast Cancer.Advances in experimental medicine and biology · 2025Review
- Decoding breast cancer treatment resistance through genetic, epigenetic, and immune-regulatory mechanisms: from molecular insights to translational perspectives.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Targeting CD200 in Breast Cancer: Opportunities and Challenges in Immunotherapeutic Strategies.International journal of molecular sciences · 2024Review
- Improving the Prognostic and Predictive Value of Circulating Tumor Cell Enumeration: Is Longitudinal Monitoring the Answer?International journal of molecular sciences · 2024Review
- Advancements and applications of single-cell multi-omics techniques in cancer research: Unveiling heterogeneity and paving the way for precision therapeutics.Biochemistry and biophysics reports · 2024Review
- Breast Cancer Immunity: It is TIME for the Next Chapter.Cold Spring Harbor perspectives in medicine · 2024Review
- Full-length isoform concatenation sequencing to resolve cancer transcriptome complexity.BMC genomics · 2024Article
- Predictive and prognostic biomarkers of bone metastasis in breast cancer: current status and future directions.Cell & bioscience · 2023Review
- New mouse genetic model of breast cancer from IKKα defects in dendritic cells revealed by single-cell RNA sequencing.Cell discovery · 2023Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Acquired resistance to targeted cancer therapy is a significant clinical challenge. In parallel with clinical trials combining CDK4/6 inhibitors to treat HER2+ breast cancer, we sought to prospectively model tumor evolution in response to this regimen in vivo and identify a clinically actionable strategy to combat drug resistance. Despite a promising initial response, acquired resistance emerges rapidly to the combination of anti-HER2/neu antibody and CDK4/6 inhibitor Palbociclib. Using high-throughput single-cell profiling over the course of treatments, we reveal a distinct immunosuppressive immature myeloid cell (IMC) population to infiltrate the resistant tumors. Guided by single-cell transcriptome analysis, we demonstrate that combination of IMC-targeting tyrosine kinase inhibitor cabozantinib and immune checkpoint blockade enhances anti-tumor immunity, and overcomes the resistance. Furthermore, sequential combinatorial immunotherapy enables a sustained control of the fast-evolving CDK4/6 inhibitor-resistant tumors. Our study demonstrates a translational framework for treating rapidly evolving tumors through preclinical modeling and single-cell analyses.
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