ArticleOncotarget2015
The oncogenic receptor ErbB2 modulates gemcitabine and irinotecan/SN-38 chemoresistance of human pancreatic cancer cells via hCNT1 transporter and multidrug-resistance associated protein MRP-2.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 41 citations in OpenAlex.
- Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma.Scientific reports · 2019Trial
- Integrative Genomics Reveals Causal Pleiotropy and Therapeutic Opportunities at the Interface of Acute Pancreatitis and Infection.Journal of hepato-biliary-pancreatic sciences · 2026Article
- Overcoming resistance to antibody-drug conjugates: from mechanistic insights to cutting-edge strategies.Journal of hematology & oncology · 2025Review
- Jorunnamycin A induces apoptosis in pancreatic ductal adenocarcinoma cells, spheroids, and patient-derived organoids by modulating KRAS-mediated survival pathways.Scientific reports · 2025Article
- Unraveling the Mechanism of Curculiginis Rhizoma in Suppressing Cisplatin Resistance in Non-Small Cell Lung Cancer: An Experimental Study.OncoTargets and therapy · 2024Article
- Prior irinotecan exposure does not preclude benefit to liposomal irinotecan in patients with metastatic pancreatic ductal adenocarcinoma.Cancer medicine · 2023Observational
- Role of Intracellular and Extracellular Annexin A1 in MIA PaCa-2 Spheroids Formation and Drug Sensitivity.Cancers · 2022Article
- Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment.Nature genetics · 2022Article
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- MUC4 enhances gemcitabine resistance and malignant behaviour in pancreatic cancer cells expressing cancer-associated short O-glycans.Cancer letters · 2021Article
- Diagnostic, Predictive and Prognostic Molecular Biomarkers in Pancreatic Cancer: An Overview for Clinicians.Cancers · 2021Review
- Targeted Therapies for Pancreatic Cancer: Overview of Current Treatments and New Opportunities for Personalized Oncology.Cancers · 2021Review
- Circular RNA in pancreatic cancer: a novel avenue for the roles of diagnosis and treatment.Theranostics · 2021Review
- Concentrative Nucleoside Transporter 3 Is Located on Microvilli of Vaginal Epithelial Cells.ACS omega · 2020Article
- CircRNAs in anticancer drug resistance: recent advances and future potential.Molecular cancer · 2020Review
- Nanoparticle delivery of a pH-sensitive prodrug of doxorubicin and a mitochondrial targeting VES-HScientific reports · 2020Article
- Article
- SRPX2 boosts pancreatic cancer chemoresistance by activating PI3K/AKT axis.Open medicine (Warsaw, Poland) · 2020Article
- Chemoresistance in Pancreatic Cancer.International journal of molecular sciences · 2019Review
- Wnt/β-Catenin Signaling: The Culprit in Pancreatic Carcinogenesis and Therapeutic Resistance.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic adenocarcinoma (PDAC) is one of the most deadly cancers because of a lack of early diagnostic markers and efficient therapeutics. The fluorinated analog of deoxycytidine, gemcitabine and emerging FOLFIRINOX protocol (5-fluorouracil (5-FU), irinotecan/SN-38, oxaliplatin and leucovorin) are the main chemotherapies to treat PDAC. The ErbB2/HER2 oncogenic receptor is commonly overexpressed in PDAC. In this context, we aimed to decipher the ErbB2-mediated mechanisms of chemoresistance to the two main chemotherapy protocols used to treat PDAC.ErbB2 knocking down (KD) in CAPAN-1 and CAPAN-2 cells led to an increased sensitivity to gemcitabine and an increased resistance to irinotecan/SN-38 both in vitro and in vivo (subcutaneous xenografts) This was correlated to an increase of hCNT1 and hCNT3 transporters and ABCG2, MRP1 and MRP2 ATP-binding cassette transporters expression and resistance to cell death. We also show that MRP2 is repressed following activation of JNK, Erk1/2 and NF-κB pathways by ErbB2. Finally, in datasets of human PDAC samples, ErbB2 and MRP2 expression was conversely correlated. Altogether, we propose that ErbB2 mediates several intracellular mechanisms linked to PDAC cell chemoresistance that may represent potential targets in order to ameliorate chemotherapy response and allow stratification of patients eligible for either gemcitabine or FOLFIRINOX treatment.
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