ArticleCancer research2024
AXL/WRNIP1 Mediates Replication Stress Response and Promotes Therapy Resistance and Metachronous Metastasis in HER2+ Breast Cancer.
Article in Cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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.
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Who cites it
19 citing papers in PubMed, 13 citations in OpenAlex.
- Multi-omics graph attention network reveals neuro-immune-tumor pathways in breast cancer liver depression syndrome.Frontiers in immunology · 2026Trial
- A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.Annals of medicine · 2026Review
- Window-of-Opportunity Study Utilizing Preoperative Cetuximab in Patients with Head and Neck Cancer.Cancer research communications · 2026Article
- SERINC2-mediated phosphatidylserine remodeling activates protrusion-localized AXL signaling to promote brain metastasis.Cell reports · 2026Article
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- A phosphorylation switch at MRE11 links ATM-ATR and calcium signaling to safeguard stalled replication fork stability.Research square · 2026Article
- SLC25A1 upregulation promotes HNSCC cisplatin resistance via H3K27ac-mediated cellular senescence.NPJ precision oncology · 2026Article
- AXL-SHC1 signaling axis mediates adaptive resistance to HER2-targeted tyrosine kinase inhibitors in HER2-aberrant lung and gastric cancers.NPJ precision oncology · 2026Article
- The significance of immunogenic cell death related prognostic gene markers in colorectal cancer prognosis and antitumor immunity.Scientific reports · 2026Article
- [Role of Receptor Tyrosine Kinase AXL in Cancer Targeted Therapy Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- RTK AXL and its Isoforms: Regulation and Implications in Cancer.Current medicinal chemistry · 2026Review
- DLBCL Cells Emerge after CD19 CAR T Cells with Cross-Antigen Resistance and a Gene Signature Predictive of Clinical CAR T-cell Response.Blood cancer discovery · 2025Article
- Cytosolic DNA and intracellular CaDNA repair · 2025Review
- Proteolysis of TAM receptors in autoimmune diseases and cancer: what does it say to us?Cell death & disease · 2025Review
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- AXL: shapers of tumor progression and immunosuppressive microenvironments.Molecular cancer · 2025Review
- The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Article
- Dendritic polylysine co-delivery of paclitaxel and siAXL enhances the sensitivity of triple-negative breast cancer chemotherapy.Frontiers in bioengineering and biotechnology · 2024Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Therapy resistance and metastatic progression are primary causes of cancer-related mortality. Disseminated tumor cells possess adaptive traits that enable them to reprogram their metabolism, maintain stemness, and resist cell death, facilitating their persistence to drive recurrence. The survival of disseminated tumor cells also depends on their ability to modulate replication stress in response to therapy while colonizing inhospitable microenvironments. In this study, we discovered that the nuclear translocation of AXL, a TAM receptor tyrosine kinase, and its interaction with WRNIP1, a DNA replication stress response factor, promotes the survival of HER2+ breast cancer cells that are resistant to HER2-targeted therapy and metastasize to the brain. In preclinical models, knocking down or pharmacologically inhibiting AXL or WRNIP1 attenuated protection of stalled replication forks. Furthermore, deficiency or inhibition of AXL and WRNIP1 also prolonged metastatic latency and delayed relapse. Together, these findings suggest that targeting the replication stress response, which is a shared adaptive mechanism in therapy-resistant and metastasis-initiating cells, could reduce metachronous metastasis and enhance the response to standard-of-care therapies. SIGNIFICANCE: Nuclear AXL and WRNIP1 interact and mediate replication stress response, promote therapy resistance, and support metastatic progression, indicating that targeting the AXL/WRNIP1 axis is a potentially viable therapeutic strategy for breast cancer.
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What OpenQuestion 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 OpenQuestion graph.