通过SHP2/PI3K途径增强KRAS G12D抑制剂在胰腺癌中的敏感性

IF 2.8 4区医学 Q2 ONCOLOGY

Medical Oncology Pub Date : 2025-03-27 DOI:10.1007/s12032-025-02683-8

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

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引用次数: 0

摘要

在40%的病例中发现了KRAS G12D突变的胰腺癌，其治疗具有挑战性。MRTX1133是一种非共价KRAS G12D抑制剂，显示出治疗前景，但面临耐药问题。我们的研究将MRTX1133与SHP2抑制剂SHP099或PI3K抑制剂buparisib联合使用，显示出协同抑制胰腺癌细胞生长和增强凋亡的作用。这些联合疗法可以改善胰腺癌KRAS G12D突变患者的临床结果。

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

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.

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来源期刊

Medical Oncology 医学-肿瘤学

CiteScore

4.20

自引率

2.90%

发文量

259

审稿时长

1.4 months

期刊介绍： Medical Oncology (MO) communicates the results of clinical and experimental research in oncology and hematology, particularly experimental therapeutics within the fields of immunotherapy and chemotherapy. It also provides state-of-the-art reviews on clinical and experimental therapies. Topics covered include immunobiology, pathogenesis, and treatment of malignant tumors.