ArticleJCI insight2020
Irreversible JNK1-JUN inhibition by JNK-IN-8 sensitizes pancreatic cancer to 5-FU/FOLFOX chemotherapy.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
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Who cites it
19 citing papers in PubMed.
- Cancer-Associated Fibroblast-Derived Sphingosine-1-Phosphate Activates a MALL-SDC4 Axis to Facilitate Perineural Invasion in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Matrix stiffness-induced IKBKE and MAPK8 signaling drives a phenotypic switch from DCIS to invasive breast cancer.Cell communication and signaling : CCS · 2025Article
- Tumor-Intrinsic Kinome Landscape of Pancreatic Cancer Reveals New Therapeutic Approaches.Cancer discovery · 2025Article
- Beyond endocrine resistance: estrogen receptor (ESR1) activating mutations mediate chemotherapy resistance through the JNK/c-Jun MDR1 pathway in breast cancer.Breast cancer research and treatment · 2025Article
- Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells.Cell reports · 2024Article
- A Histone Methylation-MAPK Signaling Axis Drives Durable Epithelial-Mesenchymal Transition in Hypoxic Pancreatic Cancer.Cancer research · 2024Article
- Myofibroblastic cancer-associated fibroblast subtype heterogeneity in pancreatic cancer.Journal of surgical oncology · 2024Article
- Article
- Proteomic Profiling of Chemotherapy Responses in FOLFOX-Resistant Colorectal Cancer Cells.International journal of molecular sciences · 2023Article
- Silencing circPalm2 inhibits sepsis-induced acute lung injury by sponging miR-376b-3p and targeting MAP3K1.Toxicological research · 2023Article
- Article
- Curcumin Derivative C66 Suppresses Pancreatic Cancer Progression through the Inhibition of JNK-Mediated Inflammation.Molecules (Basel, Switzerland) · 2022Article
- JNK inhibitor IX restrains pancreatic cancer through p53 and p21.Frontiers in oncology · 2022Article
- Exploration of the System-Level Mechanisms of the Herbal Drug FDY003 for Pancreatic Cancer Treatment: A Network Pharmacological Investigation.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Stress-activated kinases as therapeutic targets in pancreatic cancer.World journal of gastroenterology · 2021Review
- Irreversible JNK blockade overcomes PD-L1-mediated resistance to chemotherapy in colorectal cancer.Oncogene · 2021Article
- Modeling pancreatic cancer in mice for experimental therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death.Nature communications · 2021Observational
- CRTC1/MAML2 directs a PGC-1α-IGF-1 circuit that confers vulnerability to PPARγ inhibition.Cell reports · 2021Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Over 55,000 people in the United States are diagnosed with pancreatic ductal adenocarcinoma (PDAC) yearly, and fewer than 20% of these patients survive a year beyond diagnosis. Chemotherapies are considered or used in nearly every PDAC case, but there is limited understanding of the complex signaling responses underlying resistance to these common treatments. Here, we take an unbiased approach to study protein kinase network changes following chemotherapies in patient-derived xenograft (PDX) models of PDAC to facilitate design of rational drug combinations. Proteomics profiling following chemotherapy regimens reveals that activation of JNK-JUN signaling occurs after 5-fluorouracil plus leucovorin (5-FU + LEU) and FOLFOX (5-FU + LEU plus oxaliplatin [OX]), but not after OX alone or gemcitabine. Cell and tumor growth assays with the irreversible inhibitor JNK-IN-8 and genetic manipulations demonstrate that JNK and JUN each contribute to chemoresistance and cancer cell survival after FOLFOX. Active JNK1 and JUN are specifically implicated in these effects, and synergy with JNK-IN-8 is linked to FOLFOX-mediated JUN activation, cell cycle dysregulation, and DNA damage response. This study highlights the potential for JNK-IN-8 as a biological tool and potential combination therapy with FOLFOX in PDAC and reinforces the need to tailor treatment to functional characteristics of individual tumors.
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