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January 22, 2026Cancer ResearchOpen Access

KRASG12R-Mutant Pancreatic Cancer Features Limited ERK/MAPK Transcriptional Activity and a Distinctive Tumor Microenvironment

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Authors

RBRachel A. BurgeMedical University of South CarolinaOROzgun Le RouxDuke UniversityOPOlesja Popow

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Implication

Genetically engineered mouse models show that KRASG12R alters tumor behavior and microenvironment in pancreatic cancer, suggesting new therapeutic targets.

Key Points

  • The study aims to understand why KRASG12R mutations in pancreatic cancer lead to better outcomes compared to KRASG12D mutations.
  • Developed a genetically engineered mouse model with KRASG12R and p53R172H mutations.
  • Compared tumorigenesis and signaling mechanisms in KRASG12R and KRASG12D models.
  • Analyzed human PDAC cell lines and patient-derived xenografts.
  • KRASG12R models showed only 10% tumor development after one year compared to rapid disease in KRASG12D models.
  • KRASG12R had reduced ERK/MAPK nuclear translocation and transcriptional output.
  • Altered tumor microenvironment in KRASG12R included less collagen and lower metastatic activity.

Cite This Study

Burge et al. (2026) studied this question.

synapsesocial.com/papers/6971bd6a642b1836717e2142https://doi.org/10.1158/0008-5472.can-25-2630
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