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

共 50 条

[41] Dual Inhibition of KRASG12D and Pan-ERBB Is Synergistic in Pancreatic Ductal Adenocarcinoma
Gulay, Kevin Christian Montecillo
Zhang, Xinlian
Pantazopoulou, Vasiliki
Patel, Jay
Esparza, Edgar
Pran Babu, Deepa Sheik
Ogawa, Satoshi
Weitz, Jonathan
Ng, Isabella
Mose, Evangeline S.
Pu, Minya
Engle, Dannielle D.
Lowy, Andrew M.
Tiriac, Herve
CANCER RESEARCH, 2023, 83 (18) : 3001 - 3012
[42] Improving the efficacy of dual ERK-MAPK and autophagy inhibition as a therapeutic strategy for pancreatic ductal adenocarcinoma
DeLiberty, Jonathan M.
Roach, Mallory K.
Pieper, Noah L.
Drizyte-Miller, Kristina
Schechter, Elyse G.
Yang, Runying
Der, Channing J.
Cox, Adrienne D.
Stalnecker, Clint A.
Bryant, Kirsten L.
CANCER RESEARCH, 2024, 84 (02)
[43] Dual oxidase expression is epigenetically silenced in pancreatic ductal adenocarcinoma
Gibson, Adrienne
O'Leary, Brianne
Du, Juan
Chan, Carlos
Cullen, Joseph
FREE RADICAL BIOLOGY AND MEDICINE, 2018, 128 : S71 - S72
[44] Screening and validating the core biomarkers in patients with pancreatic ductal adenocarcinoma
Li, Yan
Zhu, Yuzhang
Dai, Guiping
Wu, Dongjuan
Gao, Zhenzhen
Zhang, Lei
Fan, Yaohua
MATHEMATICAL BIOSCIENCES AND ENGINEERING, 2020, 17 (01) : 910 - 927
[45] Pancreatic ductal adenocarcinoma: Risk factors, screening, and early detection
Becker, Andrew E.
Hernandez, Yasmin G.
Frucht, Harold
Lucas, Aimee L.
WORLD JOURNAL OF GASTROENTEROLOGY, 2014, 20 (32) : 11182 - 11198
[46] Screening for Pancreatic Ductal Adenocarcinoma: Are We Asking the Impossible?-Letter
Katona, Bryson W.
Brand, Randall E.
Canto, Marcia I.
Chak, Amitabh
Farrell, James J.
Kastrinos, Fay
Rustgi, Anil K.
Stoffel, Elena M.
Syngal, Sapna
Goggins, Michael
CANCER PREVENTION RESEARCH, 2021, 14 (10) : 973 - 974
[47] MAPK inhibition remodels antigen presentation in pancreatic ductal adenocarcinoma
Creech, Amanda L.
Le, Thuc M.
Abt, Evan R.
Capri, Joseph R.
Donahue, Timothy R.
Radu, Caius G.
CANCER RESEARCH, 2022, 82 (12)
[48] FAK inhibition radiosensitizes pancreatic ductal adenocarcinoma cells in vitro
A. Allam Mohamed
Andreas Thomsen
Marie Follo
Costantinos Zamboglou
Peter Bronsert
Hanan Mostafa
Aber Amen
Mohamed Mekawy
Anca L. Grosu
Thomas B. Brunner
Strahlentherapie und Onkologie, 2021, 197 : 27 - 38
[49] FAK inhibition radiosensitizes pancreatic ductal adenocarcinoma cells in vitro
Mohamed, A. Allam
Thomsen, Andreas
Follo, Marie
Zamboglou, Costantinos
Bronsert, Peter
Mostafa, Hanan
Amen, Aber
Mekawy, Mohamed
Grosu, Anca L.
Brunner, Thomas B.
STRAHLENTHERAPIE UND ONKOLOGIE, 2021, 197 (01) : 27 - 38
[50] CXCR2 Inhibition to Combat Pancreatic Ductal Adenocarcinoma
不详
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2016, 100 (03) : 205 - 205

← 1 2 3 4 5 →