ArticleOncogene2020
Feedback activation of EGFR is the main cause for STAT3 inhibition-irresponsiveness in pancreatic cancer cells.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 36 citations in OpenAlex.
- Targeting adaptive EGFR feedback enhances the therapeutic efficacy of RMC-6236 in cholangiocarcinoma.Experimental hematology & oncology · 2026Article
- ERK1/2 hijack STAT3 via Thr714 phosphorylation to suppress gene expression.Cell communication and signaling : CCS · 2026Article
- Buddlejasaponin IV inhibits proliferation and migration via STAT3 suppression in gefitinib-resistant non-small cell lung cancer cells.BMC complementary medicine and therapies · 2026Article
- Unraveling the role of STAT3 in Cancer Cachexia: pathogenic mechanisms and therapeutic opportunities.Frontiers in endocrinology · 2025Review
- Neuroprotective Effects of STAT3 Inhibitor on Hydrogen Peroxide-Induced Neuronal Cell Death via the ERK/CREB Signaling Pathway.Neurochemical research · 2024Article
- Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines.International journal of molecular sciences · 2023Article
- Acetyl-cinobufagin suppresses triple-negative breast cancer progression by inhibiting the STAT3 pathway.Aging · 2023Article
- A Comprehensive Review of Natural Products as Therapeutic or Chemopreventive Agents against Head and Neck Squamous Cell Carcinoma Cells Using Preclinical Models.Biomedicines · 2023Review
- Free-fatty acid receptor-1 (FFA1/GPR40) promotes papillary RCC proliferation and tumor growth via Src/PI3K/AKT/NF-κB but suppresses migration by inhibition of EGFR, ERK1/2, STAT3 and EMT.Cancer cell international · 2023Article
- Blockade of STAT3/IL-4 overcomes EGFR T790M-cis-L792F-induced resistance to osimertinib via suppressing M2 macrophages polarization.EBioMedicine · 2022Article
- Article
- STAT3 pathway in cancers: Past, present, and future.MedComm · 2022Review
- IL-6/STAT3 signaling pathway regulates the proliferation and damage of intestinal epithelial cells in patients with ulcerative colitis via H3K27ac.Experimental and therapeutic medicine · 2021Article
- Cyy260, a novel small molecule inhibitor, suppresses non-small cell lung cancer cell growth via JAK2/STAT3 pathway.American journal of cancer research · 2021Article
- Novel Regulatory Factors and Small-Molecule Inhibitors of FGFR4 in Cancer.Frontiers in pharmacology · 2021Review
- Cinobufagin suppresses colorectal cancer growth via STAT3 pathway inhibition.American journal of cancer research · 2021Article
- Flubendazole Elicits Antitumor Effects by Inhibiting STAT3 and Activating Autophagy in Non-small Cell Lung Cancer.Frontiers in cell and developmental biology · 2021Article
- Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway.Journal of cellular and molecular medicine · 2021Article
- Autocrine IL-6/STAT3 signaling aids development of acquired drug resistance in Group 3 medulloblastoma.Cell death & disease · 2020Article
- Cynaropicrin Shows Antitumor Progression Potential in Colorectal Cancer Through Mediation of the LIFR/STATs Axis.Frontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer is one of the world's leading causes of cancer-related death. Activation of STAT3 has been reported as a major contributor in pancreatic cancer tumorigenesis and chemoresistance. However, treatment of advanced pancreatic cancer patients with STAT3 inhibitors often meets drug resistance and heterogeneous response. We found that EGFR activation is a main cause for resistance to STAT3 inhibitors in pancreatic cancer cells, regardless of KRAS mutation status. Mechanistically, inhibition of STAT3 promotes STAT1- and STAT4-mediated TGF-α expression, leading to activation of the EGFR pathway. Combined treatment of pancreatic cancer cells with EGFR and STAT3 inhibitors persistently blocks EGFR and STAT3 signaling, and exerts synergistic antitumor activity both in vitro and in vivo, with or without KRAS mutation. Our results indicate that reciprocal cross-talk between STAT3 and EGFR pathways is a key molecular mechanism leading to resistance in pancreatic cancer cells. Furthermore, the study shows that combined inhibition of both EGFR and STAT3 might overcome drug resistance encountered during treatment with single agent alone. This study suggests an improved therapeutic strategy, through combined treatment with STAT3 and EGFR inhibitors, for pancreatic cancer patients.
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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.