通过SHP2/PI3K通路增强胰腺癌对KRAS G12D抑制剂的敏感性
Enhancing KRAS G12D inhibitor sensitivity in pancreatic cancer through SHP2/PI3K pathway.
作者信息
Hao Man-Wei, Zhang Tian-Xing, Dong Dan, Zhou Xin, Gao Haicheng
机构信息
School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, China.
Gynaecology and Obstetrics Center, The First Hospital of Jilin University, Changchun, 130021, China.
出版信息
Med Oncol. 2025 Mar 27;42(5):139. doi: 10.1007/s12032-025-02683-8.
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.
在40%的病例中发现的具有KRAS G12D突变的胰腺癌难以治疗。MRTX1133是一种非共价KRAS G12D抑制剂，显示出治疗前景，但面临耐药性问题。我们的研究将MRTX1133与SHP2抑制剂SHP099或PI3K抑制剂Buparlisib联合使用，显示出对胰腺癌细胞生长的协同抑制作用，并增强了细胞凋亡。这些联合疗法可能会改善KRAS G12D突变胰腺癌患者的临床结局。
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