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

页码：2704 / 2715

页数：12

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