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

[21] Screening for Early Pancreatic Ductal Adenocarcinoma: An Urgent Call!
Lee, Michael Xiang
Saif, Muhammad Wasif
JOURNAL OF THE PANCREAS, 2009, 10 (02): : 104 - 108
[22] Screening for Pancreatic Ductal Adenocarcinoma: Are We Asking the Impossible?
Caldwell, Katharine E.
Conway, Alexander P.
Hammill, Chet W.
CANCER PREVENTION RESEARCH, 2021, 14 (03) : 373 - 382
[23] Screening for early pancreatic ductal adenocarcinoma in hereditary pancreatitis
Howes, N
Greenhalf, W
Neoptolemos, J
MEDICAL CLINICS OF NORTH AMERICA, 2000, 84 (03) : 719 - +
[24] A Central Role for RAF→MEK→ERK Signaling in the Genesis of Pancreatic Ductal Adenocarcinoma
Collisson, Eric A.
Trejo, Christy L.
Silva, Jillian M.
Gu, Shenda
Korkola, James E.
Heiser, Laura M.
Charles, Roch-Philippe
Rabinovich, Brian A.
Hann, Byron
Dankort, David
Spellman, Paul T.
Phillips, Wayne A.
Gray, Joe W.
McMahon, Martin
CANCER DISCOVERY, 2012, 2 (08) : 685 - 693
[25] Activating Immune Recognition in Pancreatic Ductal Adenocarcinoma via Autophagy Inhibition, MEK Blockade, and CD40 Agonism
Jiang, Honglin
Courau, Tristan
Borison, Joseph
Ritchie, Alexa J.
Mayer, Aaron T.
Krummel, Matthew F.
Collisson, Eric A.
GASTROENTEROLOGY, 2022, 162 (02) : 590 - +
[26] Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma
Mahajan, Ujjwal Mukund
Alnatsha, Ahmed
Li, Qi
Oehrle, Bettina
Weiss, Frank-Ulrich
Sendler, Matthias
Distler, Marius
Uhl, Waldemar
Fahlbusch, Tim
Goni, Elisabetta
Beyer, Georg
Chromik, Ansgar
Bahra, Markus
Klein, Fritz
Pilarsky, Christian
Gruetzmann, Robert
Lerch, Markus M.
Lauber, Kirsten
Christiansen, Nicole
Kamlage, Beate
Regel, Ivonne
Mayerle, Julia
CELLS, 2021, 10 (07)
[27] NEOADJUVANT THERAPY FOLLOWED BY SURGICAL RESSECTION IS SAFE AND EFFECTIVE IN ELDERLY PATIENTS WITH PANCREATIC DUCTAL ADENOCARCINOMA
Qiao, Guoliang
Fernandez-del Castillo, Carlos
Ferrone, Cristina R.
Sell, Naomi
Hank, Thomas P.
Lillemoe, Keith
Qadan, Motaz
GASTROENTEROLOGY, 2020, 158 (06) : S1563 - S1563
[28] Patient Preferences for Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma
Hamad, Ahmad
Crossnohere, Norah
Ejaz, Aslam
Tsung, Allan
Pawlik, Timothy M.
Sarna, Angela
Santry, Heena
Wills, Celia
Cloyd, Jordan M.
PANCREAS, 2022, 51 (06) : 657 - 662
[29] Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma
Qian, Yunzhen
Gong, Yitao
Fan, Zhiyao
Luo, Guopei
Huang, Qiuyi
Deng, Shengming
Cheng, He
Jin, Kaizhou
Ni, Quanxing
Yu, Xianjun
Liu, Chen
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2020, 13 (01)
[30] Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy
Eric A Collisson
Anguraj Sadanandam
Peter Olson
William J Gibb
Morgan Truitt
Shenda Gu
Janine Cooc
Jennifer Weinkle
Grace E Kim
Lakshmi Jakkula
Heidi S Feiler
Andrew H Ko
Adam B Olshen
Kathleen L Danenberg
Margaret A Tempero
Paul T Spellman
Douglas Hanahan
Joe W Gray
Nature Medicine, 2011, 17 : 500 - 503

← 1 2 3 4 5 →