Targeting Notch signaling in pancreatic cancer

被引:54
作者
Ristorcelli, Elodie [2 ]
Lombardo, Dominique [1 ]
机构
[1] Fac Med Marseille, INSERM, UMR 911 CR02, F-13005 Marseille, France
[2] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland
关键词
cancer; notch; pancreas; signalling; EPITHELIAL-MESENCHYMAL TRANSITION; GAMMA-SECRETASE CLEAVAGE; GENE-EXPRESSION; DOWN-REGULATION; INTRACELLULAR DOMAIN; CELL-PROLIFERATION; ACTIVATION; INHIBITION; PATHWAY; DIFFERENTIATION;
D O I
10.1517/14728221003769895
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Areas covered in this review: Our aim is to present the Notch pathway, and to describe its involvement in pancreatic pathophysiology/carcinogenesis. This pathway appeared as a prime target for pancreatic cancer therapy. In the light of the crosstalk of Notch with other survival/embryologic pathways, drugs affecting more than one pathway may have to be combined. What the reader will gain: Drugs against gamma-secretases could thus serve in cancer treatment and can be combined with drugs targeting survival pathways interplaying with Notch such as Hedgehog. Take home message: Downregulation of Notch contributes to the inhibition and apoptosis of pancreatic cancer cells whereas Hedgehog inhibition will allow for enhanced delivery of drugs to the tumor. Both pathway inhibitors appear to have synergistic effects for future therapeutics for pancreatic adenocarcinoma, once safety issues of compounds are overcome.
引用
收藏
页码:541 / 552
页数:12
相关论文
共 98 条
[11]  
Cartwright Thomas, 2008, Cancer Control, V15, P308
[12]   Regulation of the ERBB-2 promoter by RBPJ kappa and NOTCH [J].
Chen, YY ;
Fischer, WH ;
Gill, GN .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (22) :14110-14114
[13]   Distinct Biological Roles for the Notch Ligands Jagged-1 and Jagged-2 [J].
Choi, Kuicheon ;
Ahn, Young-Ho ;
Gibbons, Don L. ;
Tran, Hai T. ;
Creighton, Chad J. ;
Girard, Luc ;
Minna, John D. ;
Qin, F. Xiao-Feng ;
Kurie, Jonathan M. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (26) :17766-17774
[14]   The many facets of Notch ligands [J].
D'Souza, B. ;
Miyamoto, A. ;
Weinmaster, G. .
ONCOGENE, 2008, 27 (38) :5148-5167
[15]   Notch Signaling: Where Pancreatic Cancer and Differentiation Meet? [J].
De la O, Jean-Paul ;
Murtaugh, L. Charles .
GASTROENTEROLOGY, 2009, 136 (05) :1499-1502
[16]   Notch and Kras in pancreatic cancer At the crossroads of mutation, differentiation and signaling [J].
De La O, Jean-Paul ;
Murtaugh, L. Charles .
CELL CYCLE, 2009, 8 (12) :1860-1864
[17]   Common Activation of Canonical Wnt Signaling in Pancreatic Adenocarcinoma [J].
di Magliano, Marina Pasca ;
Biankin, Andrew V. ;
Heiser, Patrick W. ;
Cano, David A. ;
Gutierrez, Pedro J. A. ;
Deramaudt, Therese ;
Segara, Davendra ;
Dawson, Amanda C. ;
Kench, James G. ;
Henshall, Susan M. ;
Sutherland, Robert L. ;
Dlugosz, Andrzej ;
Rustgi, Anil K. ;
Hebrok, Matthias .
PLOS ONE, 2007, 2 (11)
[18]   Expression of nuclear Notch3 in pancreatic adenocarcinomas is associated with adverse clinical features, and correlates with the expression of STAT3 and phosphorylated akt [J].
Doucas, Helena ;
Mann, Christopher D. ;
Sutton, Christopher D. ;
Garcea, Guiseppe ;
Neal, Christopher P. ;
Berry, David P. ;
Manson, Margaret M. .
JOURNAL OF SURGICAL ONCOLOGY, 2008, 97 (01) :63-68
[19]   Epithelial-mesenchymal transition events during human embryonic stem cell differentiation [J].
Eastham, Angela M. ;
Spencer, Helen ;
Soncin, Francesca ;
Ritson, Sarah ;
Merry, Catherine L. R. ;
Stern, Peter L. ;
Ward, Christopher M. .
CANCER RESEARCH, 2007, 67 (23) :11254-11262
[20]   Ras pathway signals are required for notch-mediated oncogenesis [J].
Fitzgerald, K ;
Harrington, A ;
Leder, P .
ONCOGENE, 2000, 19 (37) :4191-4198