KRAS抑制剂在胰腺导管腺癌临床前模型中的肿瘤阻断作用，这一成果由宾夕法尼亚大学
该课题组人员测试了PDAC拦截主题RAS（ON）多选择性或RAS(ON) G12D选择性药理抑制剂[RAS（ON）抑制剂]对PDAC无主题模型的影响。用RAS（ON）抑制剂治疗含PanIN的小鼠，可促进癌前病变的消退，从而延迟肿瘤发作和增加总生存期（OS）。长期阻断肿瘤易发小鼠的中位生存期超过1年，而非阻断对照小鼠的中位生存期不到5个月（P < 0.0001）。通过比较RAS（ON）抑制癌症阻断和RAS（ON）抑制癌症治疗对小鼠的生存益处，小组发现RAS（ON）阻断对小鼠的生存益处更大。这些研究结果表明，药理学方法可以减少PDAC的癌前负担并提高生存率。
据介绍，胰腺上皮细胞向恶性胰腺导管腺癌（PDAC）的转化通常涉及癌前胰腺上皮内瘤变（PanINs）的进展，其中携带致癌的KRAS突变。
附：英文原文
Title: Cancer interception with KRAS inhibitors in preclinical models of pancreatic ductal adenocarcinoma
Author: Minh T. Than, Lucie Dequiedt, Rina Sor, Shreya Nair, Nune Markosyan, Emma E. Furth, Chenghua Yang, Courtney Ray-Fofana, Marie Menard, Elsa Quintana, A. Cole Edwards, Connor J. Hennessey, Austin L. Good, Liz Quinones, Yunseo Hwang, Cynthia Clendenin, Ashley L. Kiemen, Robert H. Vonderheide, Ben Z. Stanger
Issue&Volume: 2026-03-12
Abstract: Transformation of pancreatic epithelial cells to malignant pancreatic ductal adenocarcinoma (PDAC) typically involves the progression of precancerous pancreatic intraepithelial neoplasia (PanINs) bearing oncogenic KRAS mutations. Here, we tested the impact of PDAC interception using either RAS(ON) multiselective or RAS(ON) G12D-selective pharmacological inhibitors [RAS(ON) inhibitors] in mouse models of PDAC. Treatment of PanIN-bearing mice with RAS(ON) inhibitors prompted regression of premalignant lesions that translated into a delay in tumor onset and an increase in overall survival (OS). Long-term interception in tumor-prone mice resulted in a median OS of more than 1 year compared with less than 5 months in nonintercepted control mice (P < 0.0001). Comparing the survival benefits of RAS(ON) inhibition for cancer interception versus RAS(ON) inhibition for cancer treatment, we found that interception provided a greater survival benefit to mice. These findings suggest that a pharmacological approach may reduce premalignant burden and increase survival in PDAC.
DOI: aec7929
Source: https://www.science.org/doi/10.1126/science.aec7929