Variable Efficacy of the Non-covalent KRAS G12D Inhibitor (MRTX-1133) with Obesity in Murine Pancreatic Cancer

  1. Sujith Sarvesh
  2. Holly Stephens
  3. Pia Muri
  4. Henry Nnaemeka Ogbonna
  5. Jianqing Zhang
  6. Dhana Sekar Reddy Bandi
  7. Cherlene Hardy
  8. Ganji Purnachandra Nagaraju
  9. Bassel F. El-Rayes
  10. Lyse A. Norian
  11. Jeremy B. Foote
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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.

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  1. Version published to 10.21203/rs.3.rs-7871709/v1 on Research Square