Islam Mohammad Mazharul, Goertzen Andrea, Singh Pankaj K, Saha Rajib
Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
iScience. 2022 May 30;25(6):104483. doi: 10.1016/j.isci.2022.104483. eCollection 2022 Jun 17.
Pancreatic ductal adenocarcinoma (PDAC) is a major research focus because of its poor therapy response and dismal prognosis. PDAC cells adapt their metabolism to the surrounding environment, often relying on diverse nutrient sources. Because traditional experimental techniques appear exhaustive to find a viable therapeutic strategy, a highly curated and omics-informed PDAC genome-scale metabolic model was reconstructed using patient-specific transcriptomics data. From the model-predictions, several new metabolic functions were explored as potential therapeutic targets in addition to the known metabolic hallmarks of PDAC. Significant downregulation in the peroxisomal beta oxidation pathway, flux modulation in the carnitine shuttle system, and upregulation in the reactive oxygen species detoxification pathway reactions were observed. These unique metabolic traits of PDAC were correlated with potential drug combinations targeting genes with poor prognosis in PDAC. Overall, this study provides a better understanding of the metabolic vulnerabilities in PDAC and will lead to novel effective therapeutic strategies.
胰腺导管腺癌（PDAC）因其治疗反应不佳和预后不良而成为主要研究重点。PDAC细胞会根据周围环境调整自身代谢，常常依赖多种营养来源。由于传统实验技术似乎已穷尽，难以找到可行的治疗策略，因此利用患者特异性转录组学数据重建了一个经过高度筛选且基于组学信息的PDAC基因组规模代谢模型。从模型预测结果中，除了已知的PDAC代谢特征外，还探索了几种新的代谢功能作为潜在治疗靶点。观察到过氧化物酶体β氧化途径显著下调、肉碱穿梭系统中的通量调节以及活性氧解毒途径反应上调。PDAC这些独特的代谢特征与针对PDAC中预后不良基因的潜在药物组合相关。总体而言，本研究能更好地理解PDAC中的代谢脆弱性，并将引领新的有效治疗策略。
Zotero 插件