Novel STAT 3 inhibitors for treating gastric cancer

被引:54
作者
Cafferkey, Catherine [1 ]
Chau, Ian [1 ]
机构
[1] Royal Marsden Hosp, Gastrointestinal & Lymphoma Trials Unit, London, England
关键词
Gastric cancer; STAT3; inhibitor; ACTIVATED SIGNAL TRANSDUCER; PHASE-I; CELL-SURVIVAL; OPEN-LABEL; TRANSCRIPTION; EXPRESSION; OPB-31121; METASTASIS; TUMORIGENESIS; INFLAMMATION;
D O I
10.1080/13543784.2016.1195807
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Advanced gastric cancer has a poor prognosis, with a median survival of approximately 12 months. There is a continued need to explore the use of novel treatments for this disease. STAT3 inhibitors are under evaluation in a number of early phase trials, some showing promise in gastric cancer. Areas covered: This article explores the role of STAT 3 in gastric cancer and highlights some early phase clinical trials on STAT3 inhibition. The STAT3 protein and signalling pathway are discussed. STAT3 in the pathogenesis of gastric cancer is reviewed; pre-clinical data on the role of STAT3 in the development of cancer is presented together with early and emerging data on STAT3 inhibitors under investigation in the clinical setting. In this review, the authors searched PubMed, clinicaltrials. gov and ASCO abstracts on STAT3 inhibitors, focusing on trials recruiting gastric cancer patients. Expert opinion: Activated STAT3 in gastric cancer is correlated with poor survival. It plays a critical role in regulating tumour growth and metastases. STAT3 inhibitors are emerging as an interesting drug in gastric cancer. However, trials utilising these agents remain in their early phase with one agent currently under evaluation in the phase III setting.
引用
收藏
页码:1023 / 1031
页数:9
相关论文
共 45 条
[1]   MOLECULAR-CLONING OF APRF, A NOVEL IFN-STIMULATED GENE FACTOR-3 P91-RELATED TRANSCRIPTION FACTOR INVOLVED IN THE GP130-MEDIATED SIGNALING PATHWAY [J].
AKIRA, S ;
NISHIO, Y ;
INOUE, M ;
WANG, XJ ;
WEI, S ;
MATSUSAKA, T ;
YOSHIDA, K ;
SUDO, T ;
NARUTO, M ;
KISHIMOTO, T .
CELL, 1994, 77 (01) :63-71
[2]  
[Anonymous], 2016 GASTR CANC S M
[3]  
[Anonymous], J CLIN ONCOL
[4]  
[Anonymous], J CLIN ONCOL S4S
[5]  
[Anonymous], J CLIN ONCOL
[6]  
[Anonymous], J CLIN ONCOL
[7]  
[Anonymous], 2016 GASTR CANC S
[8]  
Bang YJ, 2010, LANCET, V376, P1302
[9]   Phase Ib/II study of cancer stem cell (CSC) inhibitor BBI608 combined with paclitaxel in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. [J].
Becerra, Carlos ;
Stephenson, Joe ;
Jonker, Derek J. ;
Cohn, Allen Lee ;
Asmis, Timothy R. ;
Bekaii-Saab, Tanios S. ;
Conkling, Paul R. ;
Garbo, Lawrence E. ;
Lenz, Heinz-Josef ;
Richards, Donald A. ;
Spira, Alexander I. ;
Mikhail, Sameh ;
Goodwin, Rachel Anne ;
Yoon, Harry H. ;
Hume, Stephanie ;
Hitron, Matthew ;
Li, Chiang .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (15)
[10]   Phase 1, open-label, dose-escalation, and pharmacokinetic study of STAT3 inhibitor OPB-31121 in subjects with advanced solid tumors [J].
Bendell, Johanna C. ;
Hong, David S. ;
Burris, Howard A., III ;
Naing, Aung ;
Jones, Suzanne F. ;
Falchook, Gerald ;
Bricmont, Patricia ;
Elekes, Agnes ;
Rock, Edwin P. ;
Kurzrock, Razelle .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2014, 74 (01) :125-130