中国科学院分子细胞科学卓越创新中心高栋小组取得一项新突破。他们的研究开发出了胰腺癌类器官生物库将多组学特征与他汀类药物联合治疗的治疗反应和临床评估联系起来。该研究于2025年8月13日发表于国际一流学术期刊《细胞—干细胞》杂志上。

研究组建立了260个胰腺癌类器官系，随后进行了广泛的多组学分析和治疗敏感性评估。综合分析发现了6个新的编码和35个非编码驱动候选程序。研究人员发现了2794个与药物敏感性相关的多组学特征和322个与辐射敏感性相关的特征。药物基因组学分析显示，类化学耐药器官在蛋白质糖基化和胆固醇代谢途径中表现出富集。

值得注意的是，他汀类药物有效靶向耐药PDAC类器官。他汀类药物治疗可减弱PDAC类器官中的蛋白糖基化、胆固醇水平和上皮-间质转化（EMT）特征。该课题组研究人员开展了一项单中心、单臂、2期临床试验（NCT06241352），联合阿托伐他汀与化疗治疗晚期胰腺癌患者。在37例患者中，26例（70.3%）显示出反应，肿瘤标志物下降超过20%，表明在这一具有挑战性的患者群体中有持久的反应和潜在的临床益处。

据了解，化疗仍然是胰腺导管腺癌（PDAC）的主要治疗方法，但大多数患者最终产生耐药性。

附：英文原文

Title: A pancreatic cancer organoid biobank links multi-omics signatures to therapeutic response and clinical evaluation of statin combination therapy

Author: Yunguang Li, Shijie Tang, Huan Wang, Hongwen Zhu, Yurun Lu, Yehan Zhang, Shiwei Guo, Juan He, Yikai Li, Yi Zhang, Xiaohan Shi, Yuanxiang Miao, Chaoliang Zhong, Yiqin Zhu, Yi Ju, Yuejia Liu, Maoyuan Sun, Yong Wang, Luonan Chen, Hu Zhou, Gang Jin, Dong Gao

Issue&Volume: 2025-08-13

Abstract: Chemotherapy remains the primary treatment for pancreatic ductal adenocarcinoma (PDAC), but most patients ultimately develop resistance. Here, we established 260 pancreatic cancer organoid lines, followed by extensive multi-omics profiling and therapeutic sensitivity assessments. Integrated analyses uncovered 6 novel coding and 35 noncoding driver candidates. We discovered 2,794 multi-omics features associated with drug sensitivity and 322 features linked to radiation sensitivity. Pharmacogenomic analyses revealed that chemoresistant organoids exhibited enrichment in protein glycosylation and cholesterol metabolism pathways. Notably, statins effectively targeted chemoresistant PDAC organoids. Statin treatment attenuated protein glycosylation, cholesterol levels, and the epithelial-to-mesenchymal transition (EMT) signature in PDAC organoids. We conducted a single-center, single-arm, phase 2 clinical trial (NCT06241352) combining atorvastatin with chemotherapy in patients with advanced pancreatic cancer. Among 37 patients, 26 (70.3%) demonstrated a response, with tumor markers decreasing by more than 20%, suggesting durable responses and potential clinical benefits in this challenging patient population.

DOI: 10.1016/j.stem.2025.07.008

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00265-6