Variable efficacy of the non-covalent KRASG12D inhibitor (MRTX-1133) with obesity in murine pancreatic cancer

npj Precision Oncology 2026 Open access

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Authors: Sujith Sarvesh, Holly R. Stephens, Pia Muri, Henry Nnaemeka Ogbonna, Jianqing Zhang, Karen Aikhionbare, Dhana Sekhar Reddy Bandi, Cherlene Hardy, Ganji Purnachandra Nagaraju, Bassel F. El‐Rayes, Lyse A. Norian, Jeremy B. Foote
DOI: 10.1038/s41698-026-01493-z
Cited by: 0
References: 26

Abstract

Abstract Diet-induced obesity (DIO) promotes pancreatic tumor progression, immunosuppression, and resistance to chemotherapy. The impact of DIO on efficacy of KRAS G12D -specific inhibitor MRTX1133 in syngeneic mouse PDAC cell lines implanted into in lean and DIO mice was evaluated. MRTX1133 induced regression in syngeneic murine PDAC models, irrespective of immune microenvironment composition or body condition, yet, DIO promoted immunosuppression through recruitment of gMDSC into T-cell inflamed TME, reversing control of microscopic disease.

Fields of Study & Subjects

Fibroblast Growth Factor Research Protein Tyrosine Phosphatases Metabolism Diabetes and Cancer

Publication details

Journal / source
npj Precision Oncology
Publisher
Springer Science and Business Media LLC
Volume
10
Issue
1
Publication date
8 June 2026
Language
EN