ArticleGastroenterology2026
Blockade of Tumor TAK1 Induces DNA Damage and Immunogenic cGAS-STING Pathway Activation in Pancreatic Cancer.
Article in Gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND &
aimsTargeting the transforming growth factor-β (TGF-β) pathway to reverse the immunologically "cold" tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) remains clinically unsuccessful, warranting novel therapeutic strategies.
methodsWe performed multiplex immunohistochemistry on human PDAC samples to correlate cell-type-specific TGF-β pathway activation and CD8
resultsWe found TGF-β-activated kinase 1 (TAK1, Map3k7) to be aberrantly activated in PDAC cells and correlates with T-cell dysfunction. Pharmacological inhibition with Takinib, or genetic deletion of tumor Map3k7 in an autochthonous p48-Cre/Trp53
conclusionsWe uncover TAK1 as a critical mediator in maintaining genomic integrity and highlight its potential as a therapeutic target to induce an inflamed tumor microenvironment that sensitizes PDAC to immune checkpoint blockade.
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