ArticleScience signaling2016
JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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
36 citing papers in PubMed, 63 citations in OpenAlex.
- A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2017Trial
- Multi-omic cell free DNA profiles of cerebral spinal fluid from lung cancer metastasis to the brain.NAR cancer · 2026Article
- Mitochondrial translocation of MDM2 and TFAM reprograms metabolism in treatment-refractory cancers.NPJ precision oncology · 2026Article
- Nanopore-based cell-free DNA fragmentation and methylation profiles from the cerebral spinal fluid of patients with lung cancer brain metastases.bioRxiv : the preprint server for biology · 2025Article
- The importance of integrated therapies on cancer: Silibinin, an old and new molecule.Oncotarget · 2024Review
- An Overview of EGFR Mechanisms and Their Implications in Targeted Therapies for Glioblastoma.International journal of molecular sciences · 2023Review
- An intrinsic purine metabolite AICAR blocks lung tumour growth by targeting oncoprotein mucin 1.British journal of cancer · 2023Article
- Protein degradation: expanding the toolbox to restrain cancer drug resistance.Journal of hematology & oncology · 2023Review
- Molecular pathways, resistance mechanisms and targeted interventions in non-small-cell lung cancer.Molecular biomedicine · 2022Review
- Review
- FGFR leads to sustained activation of STAT3 to mediate resistance to EGFR-TKIs treatment.Investigational new drugs · 2021Article
- The Root Extract ofInternational journal of molecular sciences · 2021Article
- AKT1 E17K Inhibits Cancer Cell Migration by Abrogating β-Catenin Signaling.Molecular cancer research : MCR · 2021Article
- Antitumour immunity regulated by aberrant ERBB family signalling.Nature reviews. Cancer · 2021Review
- Programmed death-ligand 1 expression level as a predictor of EGFR tyrosine kinase inhibitor efficacy in lung adenocarcinoma.Translational lung cancer research · 2021Article
- Updated Insights on EGFR Signaling Pathways in Glioma.International journal of molecular sciences · 2021Review
- Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020Review
- Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer.Antibodies (Basel, Switzerland) · 2020Article
- Current Strategies for Treating NSCLC: From Biological Mechanisms to Clinical Treatment.Cancers · 2020Review
- PIM1 inhibitor synergizes the anti-tumor effect of osimertinib via STAT3 dephosphorylation in EGFR-mutant non-small cell lung cancer.Annals of translational medicine · 2020Article
Corrections and comments
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Authors and funding
25 authors at 2 institutions in 1 country.
Funding
Abstract
Lung adenocarcinomas with mutant epidermal growth factor receptor (EGFR) respond to EGFR-targeted tyrosine kinase inhibitors (TKIs), but resistance invariably occurs. We found that the Janus kinase (JAK)/signal transduction and activator of transcription 3 (STAT3) signaling pathway was aberrantly increased in TKI-resistant EGFR-mutant non-small cell lung cancer (NSCLC) cells. JAK2 inhibition restored sensitivity to the EGFR inhibitor erlotinib in TKI-resistant cell lines and xenograft models of EGFR-mutant TKI-resistant lung cancer. JAK2 inhibition uncoupled EGFR from its negative regulator, suppressor of cytokine signaling 5 (SOCS5), consequently increasing EGFR abundance and restoring the tumor cells' dependence on EGFR signaling. Furthermore, JAK2 inhibition led to heterodimerization of mutant and wild-type EGFR subunits, the activity of which was then blocked by TKIs. Our results reveal a mechanism whereby JAK2 inhibition overcomes acquired resistance to EGFR inhibitors and support the use of combination therapy with JAK and EGFR inhibitors for the treatment of EGFR-dependent NSCLC.
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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.