Drosophila Screening Identifies Dual Inhibition of MEK and AURKB as an Effective Therapy for Pancreatic Ductal Adenocarcinoma

被引：4
|
作者：
Sekiya, Sho [1 ,2 ]
Fukuda, Junki [1 ,2 ]
Yamamura, Ryodai [1 ]
Ooshio, Takako [1 ]
Satoh, Yusuke [1 ]
Kosuge, Shinya [1 ,2 ]
Sato, Reo [1 ]
Hatanaka, Kanako C. [3 ]
Hatanaka, Yutaka [3 ,4 ]
Mitsuhashi, Tomoko [5 ]
Nakamura, Toru [2 ]
Matsuno, Yoshihiro [5 ]
Hirano, Satoshi [2 ]
Sonoshita, Masahiro [1 ,6 ]
机构：
[1] Hokkaido Univ, Inst Genet Med, Div Biomed Oncol, Sapporo 0600815, Japan
[2] Hokkaido Univ, Fac Med, Dept Gastroenterol Surg 2, Sapporo, Japan
[3] Hokkaido Univ Hosp, Ctr Dev Adv Diagnost, Sapporo, Japan
[4] Hokkaido Univ Hosp, Res Div Genome Compan Diagnost, Sapporo, Japan
[5] Hokkaido Univ Hosp, Dept Surg Pathol, Sapporo, Japan
[6] Hokkaido Univ, Global Stn Biosurfaces & Drug Discovery, Sapporo 0600812, Japan
来源：
CANCER RESEARCH | 2023年 / 83卷 / 16期
基金：
日本学术振兴会; 日本科学技术振兴机构;
关键词：
PHASE-1; DOSE-ESCALATION; AURORA-B; CANCER; KINASE; TRAMETINIB; COOPERATE; GEMCITABINE; PROGRESSION; EXPRESSION; KRAS(G12D);
D O I：
10.1158/0008-5472.CAN-22-3762
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Significant progress has been made in understanding the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) by generating and using murine models. To accelerate drug discovery by identifying novel therapeutic targets on a systemic level, here we generated a Drosophila model mimicking the alterations), which is associated with the worst prognosis in patients. The '4-hit' flies displayed epithelial transformation and decreased survival. Comprehensive genetic screening of their entire kinome revealed kinases including MEK and AURKB as therapeutic targets. Consistently, a combination of the MEK
引用
收藏
页码：2704 / 2715
页数：12
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