ArticleOncogene2013
Gemcitabine triggers a pro-survival response in pancreatic cancer cells through activation of the MNK2/eIF4E pathway.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04098081 (1911GCCC), which is not on this map. Cited by 83 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.
1911GCCC: Open Label, Phase 2 Trial of Galeterone Combined With Gemcitabine for Patients With Metastatic Pancreatic Adenocarcinoma Refractory to Standard Chemotherapy
Who cites it
83 citing papers in PubMed, 132 citations in OpenAlex.
- RAB1A is a novel vulnerability in uveal melanoma revealed by dual inhibition of MNK1/2 and mTOR.Cell death and differentiation · 2026Article
- U2 snRNP inhibition hampers pancreatic cancer cell viability by disrupting DNA repair proficiency and mitotic checkpoint integrity.Journal of experimental & clinical cancer research : CR · 2026Article
- K11- and K29-ubiquitination-mediated nuclear translocation of glycolytic enzyme aldolase A promotes pancreatic cancer progression by NF-κB activation.Cell death and differentiation · 2026Article
- Safety and efficacy of the MNK/VEGFR inhibitor JDB153 combined with the anti-PD-1 antibody serplulimab in patients with advanced pancreatic cancer refractory to standard treatment: a single-arm, phase Ib/II study protocol.Frontiers in pharmacology · 2026Article
- SRSF1-mediated alternative splicing regulates bladder cancer progression and cisplatin sensitivity through HIF1A/BNIP3/mitophagy axis.Journal of translational medicine · 2025Article
- Article
- MicroRNA-150-3p enhances the antitumour effects of CGP57380 and is associated with a favourable prognosis in non-small cell lung cancer.Scientific reports · 2025Article
- MNK: A Novel Promising Target for Cancer Immunotherapy.Current medicinal chemistry · 2025Review
- Exploiting Translation Machinery for Cancer Therapy: Translation Factors as Promising Targets.International journal of molecular sciences · 2024Review
- Spliceosomic dysregulation in pancreatic cancer uncovers splicing factors PRPF8 and RBMX as novel candidate actionable targets.Molecular oncology · 2024Article
- An alternative splicing signature defines the basal-like phenotype and predicts worse clinical outcome in pancreatic cancer.Cell reports. Medicine · 2024Article
- Splicing alterations in pancreatic ductal adenocarcinoma: a new molecular landscape with translational potential.Journal of experimental & clinical cancer research : CR · 2023Review
- Targeting drug-tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells.MedComm · 2023Review
- Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer.Journal of medicinal chemistry · 2023Article
- Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer.bioRxiv : the preprint server for biology · 2023Article
- N7-methylguanosine modification: from regulatory roles to therapeutic implications in cancer.American journal of cancer research · 2023Review
- Targeting pre-mRNA splicing in cancers: roles, inhibitors, and therapeutic opportunities.Frontiers in oncology · 2023Review
- Systematic Identification of the RNA-Binding Protein STAU2 as a Key Regulator of Pancreatic Adenocarcinoma.Cancers · 2022Article
- Synergistic Antitumoral Effect of Epigenetic Inhibitors and Gemcitabine in Pancreatic Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Inhibition of MNKs promotes macrophage immunosuppressive phenotype to limit CD8+ T cell antitumor immunity.JCI insight · 2022Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplastic disease. Gemcitabine, the currently used chemotherapeutic drug for PDAC, elicits only minor benefits, because of the development of escape pathways leading to chemoresistance. Herein, we aimed at investigating the involvement of the mitogen activating protein kinase interacting kinase (MNK)/eIF4E pathway in the acquired drug resistance of PDAC cells. Screening of a cohort of PDAC patients by immunohistochemistry showed that eIF4E phosphorylation correlated with disease grade, early onset of disease and worse prognosis. In PDAC cell lines, chemotherapeutic drugs induced MNK-dependent phosphorylation of eIF4E. Importantly, pharmacological inhibition of MNK activity synergistically enhanced the cytostatic effect of gemcitabine, by promoting apoptosis. RNA interference (RNAi) experiments indicated that MNK2 is mainly responsible for eIF4E phosphorylation and gemcitabine resistance in PDAC cells. Furthermore, we found that gemcitabine induced the expression of the oncogenic splicing factor SRSF1 and splicing of MNK2b, a splice variant that overrides upstream regulatory pathways and confers increased resistance to the drug. Silencing of SRSF1 by RNAi abolished this splicing event and recapitulated the effects of MNK pharmacological or genetic inhibition on eIF4E phosphorylation and apoptosis in gemcitabine-treated cells. Our results highlight a novel pro-survival pathway triggered by gemcitabine in PDAC cells, which leads to MNK2-dependent phosphorylation of eIF4E, suggesting that the MNK/eIF4E pathway represents an escape route utilized by PDAC cells to withstand chemotherapeutic treatments.
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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.