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<p>Pancreatic cancer with the <i>KRAS G12D</i> mutation, found in 40% of cases, is challenging to treat. MRTX1133, a non-covalent KRAS G12D inhibitor, shows therapeutic promise but faces resistance issues. Our study combines MRTX1133 with the SHP2 inhibitor SHP099 or PI3K inhibitor Buparlisib, showing synergistic inhibition of pancreatic cancer cell growth and enhanced apoptosis. These combination therapies could improve clinical outcomes for patients with <i>KRAS G12D</i> &#xa0;mutation in&#xa0;pancreatic cancer.</p>

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Enhancing KRAS G12D inhibitor sensitivity in pancreatic cancer through SHP2/PI3K pathway

  • 期刊论文

  • 发表日期：

    2025年3月27日

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  • Man-Wei Hao,
  • Tian-Xing Zhang,
  • Dan Dong,
  • Xin Zhou,
  • Haicheng Gao

摘要

Pancreatic cancer with the KRAS G12D mutation, found in 40% of cases, is challenging to treat. MRTX1133, a non-covalent KRAS G12D inhibitor, shows therapeutic promise but faces resistance issues. Our study combines MRTX1133 with the SHP2 inhibitor SHP099 or PI3K inhibitor Buparlisib, showing synergistic inhibition of pancreatic cancer cell growth and enhanced apoptosis. These combination therapies could improve clinical outcomes for patients with KRAS G12D  mutation in pancreatic cancer.