ArticleCancer discovery2020
Oncogenic KRAS-Driven Metabolic Reprogramming in Pancreatic Cancer Cells Utilizes Cytokines from the Tumor Microenvironment.
Article in Cancer discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
157 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- Current status of KRAS G12C inhibitors in NSCLC and the potential for combination with anti-PD-(L)1 therapy: a systematic review.Frontiers in immunology · 2025Pooled it
- KRAS-G12D inhibitor HRS-4642 plus chemotherapy in advanced KRASNature medicine · 2026Trial
- The regulatory roles of non-coding RNAs in aerobic glycolysis and therapeutic potential in pancreatic ductal adenocarcinoma.Annals of medicine · 2026Review
- Oncogenic Mutations and Tumor Microenvironment Alterations in Diffuse Large B-Cell Lymphoma With Bulky Disease.Cancer medicine · 2026Article
- Lipid metabolic reprogramming of tumor-associated macrophages drives resistance to immune checkpoint blockade in lung cancer: a narrative review of mechanisms and therapeutic strategies.Translational lung cancer research · 2026Review
- Blocking L-carnitine synthesis by meldonium prolongs the survival in mice with pancreatic cancer.iScience · 2026Article
- CDK8 remodels the tumor microenvironment and promotes resistance to KRASThe EMBO journal · 2026Article
- Oncogenic Kras targeting with MRTX1133 or Daraxonrasib specifically synergize with anti-CTLA4 to promote anti-tumor immunity in pancreatic cancer.Nature communications · 2026Article
- Silencing the Signal: The Metastasis Suppressor NDRG1 Disrupts Small Extracellular Vesicle-Mediated Crosstalk in Pancreatic Cancer.Journal of extracellular vesicles · 2026Article
- Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas: current understanding and perspectives on malignant progression.Journal of gastroenterology · 2026Review
- Acquisition of Resistance to RAS Inhibition Is Associated with the Upregulation of Macropinocytosis through Both PI3K-Dependent and -Independent Signaling.Cancer research communications · 2026Article
- Histone lactylation boosted SET8 potentiates carcinogenesis and angiogenesis of pancreatic ductal adenocarcinoma by cooperating with MTA1/NuRD complex.Journal of translational medicine · 2026Article
- KRAS and MYC synergistic inhibition: a powerful strategy targeting KRAS-mutant cancers.Molecular cancer · 2026Review
- TNFAIP6, an independent prognostic monitor and therapy target, promoted low-grade glioma recurrence and progression via JAK3-STAT6 signaling.International journal of surgery (London, England) · 2026Article
- Organoids: technology refining, current applications and future directions.Molecular biomedicine · 2026Review
- Review
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- Targeting stroma-mediated T-cell exclusion and functional exhaustion in pancreatic ductal adenocarcinoma through CXCR4 and PD-1 blockade.Frontiers in immunology · 2026Article
- KRAS-driven cytokine-metabolic crosstalk shapes immune exclusion in pancreatic ductal adenocarcinoma.Frontiers in genetics · 2026Review
- SOX8 mediates the crosstalk between KRAS and TGF-β pathways to promote the malignant progression of pancreatic cancer.American journal of cancer research · 2026Article
97 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
27 authors at 4 institutions in 1 country.
Funding
Abstract
A hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant stroma comprised of diverse cell types that enable or suppress tumor progression. Here, we explored the role of oncogenic KRAS in protumorigenic signaling interactions between cancer cells and host cells. We show that KRAS mutation (KRAS*) drives cell-autonomous expression of type I cytokine receptor complexes (IL2rγ-IL4rα and IL2rγ-IL13rα1) in cancer cells that in turn are capable of receiving cytokine growth signals (IL4 or IL13) provided by invading Th2 cells in the microenvironment. Early neoplastic lesions show close proximity of cancer cells harboring KRAS* and Th2 cells producing IL4 and IL13. Activated IL2rγ-IL4rα and IL2rγ-IL13rα1 receptors signal primarily via JAK1-STAT6. Integrated transcriptomic, chromatin occupancy, and metabolomic studies identified MYC as a direct target of activated STAT6 and that MYC drives glycolysis. Thus, paracrine signaling in the tumor microenvironment plays a key role in the KRAS*-driven metabolic reprogramming of PDAC. SIGNIFICANCE: Type II cytokines, secreted by Th2 cells in the tumor microenvironment, can stimulate cancer cell-intrinsic MYC transcriptional upregulation to drive glycolysis. This KRAS*-driven heterotypic signaling circuit in the early and advanced tumor microenvironment enables cooperative protumorigenic interactions, providing candidate therapeutic targets in the KRAS* pathway for this intractable disease.
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What OpenQuestion holds
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.