ArticleMolecular cancer2015
Synergistic anti-tumor effect of combined inhibition of EGFR and JAK/STAT3 pathways in human ovarian cancer.
Article in Molecular cancer, 2015. 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, 92 citations in OpenAlex.
- CDDO-Me Overcomes Gefitinib Resistance in NSCLC by Targeting the Src/STAT3 Axis to Induce Apoptosis and Pyroptosis.International journal of molecular sciences · 2026Article
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- Repression of EGFR by new biguanide 4C potentiated ovarian cancer to PARP inhibitors through down-regulation of BRCA2 and Rad51.Cell death & disease · 2026Article
- Unraveling the Molecular Mechanisms of Benzo(a)pyrene (BaP)-Induced Ovarian-Related Disorders: Integrating Computational Predictions and Experimental Validation.International journal of molecular sciences · 2026Article
- Inflammatory milieu and role of epigenetic modifications in high-grade serous ovarian cancer.Clinical epigenetics · 2026Review
- Article
- Obacunone alleviated the development of polycystic ovary syndrome via inhibiting STAT3 phosphorylation.Journal of ovarian research · 2025Article
- TAIII Suppresses the Growth of T790M-Mutant Non-Small-Cell Lung Cancer by Targeting the EGFR/ERK Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Inflammation and Immune Escape in Ovarian Cancer: Pathways and Therapeutic Opportunities.Journal of inflammation research · 2025Review
- Alkaloid-driven multi-target synergy ofFrontiers in pharmacology · 2025Article
- Topical Delivery of Dual Loaded Nano-Transfersomes Mediated Chemo-Photodynamic Therapy against Melanoma via Inducing Cell Cycle Arrest and Apoptosis.International journal of molecular sciences · 2024Article
- Enhancing the therapeutic efficacy of gefitinib on subcutaneously transplanted SKOV3 ovarian cancer tumors in nude mice via ultrasound‑stimulated microbubble cavitation.Experimental and therapeutic medicine · 2024Article
- Induction of Multiple Alternative Mitogenic Signaling Pathways Accompanies the Emergence of Drug-Tolerant Cancer Cells.Cancers · 2024Article
- Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery.Journal of experimental & clinical cancer research : CR · 2024Review
- Mitophagy genes in ovarian cancer: a comprehensive analysis for improved immunotherapy.Discover oncology · 2023Article
- SLC14A1 is a new biomarker in renal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Targeting receptor tyrosine kinases in ovarian cancer: Genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies.Molecular therapy oncolytics · 2023Review
- Efficacy evaluation of multi-immunotherapy in ovarian cancer: From bench to bed.Frontiers in immunology · 2022Review
- Dual inhibition of EGFR and IL-6-STAT3 signalling by miR-146b: a potential targeted therapy for epithelial ovarian cancer.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Dual Targeting EGFR and STAT3 With Erlotinib and Alantolactone Co-Loaded PLGA Nanoparticles for Pancreatic Cancer Treatment.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe EGFR signaling pathway is frequently activated in human ovarian cancer and associated with poor prognosis. However, inhibition of EGFR signaling in patients with recurrent ovarian cancer has been disappointing. It remains to be addressed whether ovarian cancer patients could benefit from targeting EGFR signaling. Here we investigated the mechanisms underlying the resistance to EGFR inhibition in ovarian cancer and developed a strategy to overcome it.
resultsWe found that treatment of human ovarian cancer cells with an EGFR inhibitor, gefitinib, resulted in increased STAT3 phosphorylation in a dose- and time-dependent manner. Inhibiting STAT3 activation with a small molecule inhibitor of JAK, an upstream kinase that phosphorylates and activates STAT3, synergistically increased the anti-tumor activity of gefitinib in vitro. Similar results were obtained when STAT3 or JAK1 expression was knocked down. In contrast, inhibiting other signaling pathways, such as AKT/mTOR, MEK or SRC, was relatively less effective. The combined treatment resulted in simultaneous attenuation of multiple survival pathways and increased inhibition of ERK pathway. In addition, the dual inhibition showed a stronger suppression of xenograft tumor growth than either single inhibition.
conclusionsOur findings demonstrate that feedback activation of STAT3 pathway might contribute to the resistance to EGFR inhibition. Combined blockade of both pathways appears to be more effective against human ovarian cancer than inhibition of each pathway alone both in vitro and in vivo. This study may provide a strategy to improve clinical benefit of targeting EGFR pathway in ovarian cancer patients.
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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.