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

来源：

EXPERT OPINION ON THERAPEUTIC TARGETS | 2010年 / 14卷 / 05期

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

页码：541 / 552

页数：12

共 98 条

[81] Notch signaling, γ-secretase inhibitors, and cancer therapy [J].

Shih, Ie-Ming ;

Wang, Tian-Li .

CANCER RESEARCH, 2007, 67 (05) :1879-1882

[82] Notch1 augments NF-κB activity by facilitating its nuclear retention [J].

Shin, HM ;

Minter, LM ;

Cho, OH ;

Gottipati, S ;

Fauq, AH ;

Golde, TE ;

Sonenshein, GE ;

Osborne, BA .

EMBO JOURNAL, 2006, 25 (01) :129-138

[83] Disruption of TGFβ signaling pathways in human pancreatic cancer cells [J].

Simeone, DM ;

Pham, T ;

Logsdon, CD .

ANNALS OF SURGERY, 2000, 232 (01) :73-80

[84] The Notch pathway in cancer:: Differentiation gone awry [J].

Sjölund, J ;

Manetopoulos, C ;

Stockhausen, MT ;

Axelson, H .

EUROPEAN JOURNAL OF CANCER, 2005, 41 (17) :2620-2629

[85] Evidence for the Notch signaling pathway on the role of estrogen in angiogenesis [J].

Soares, R ;

Balogh, G ;

Guo, S ;

Gärtner, F ;

Russo, J ;

Schmitt, F .

MOLECULAR ENDOCRINOLOGY, 2004, 18 (09) :2333-2343

[86] Aberrant activation of Notch signaling in human breast cancer [J].

Stylianou, S ;

Clarke, RB ;

Brennan, K .

CANCER RESEARCH, 2006, 66 (03) :1517-1525

[87] Notch4 intracellular domain binding to Smad3 and inhibition of the TGF-β signaling [J].

Sun, YP ;

Lowther, W ;

Kato, K ;

Bianco, C ;

Kenney, N ;

Strizzi, L ;

Raafat, D ;

Hirota, M ;

Khan, NI ;

Bargo, S ;

Jones, B ;

Salomon, D ;

Callahan, R .

ONCOGENE, 2005, 24 (34) :5365-5374

[88] Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis [J].

Tian, Hua ;

Callahan, Christopher A. ;

DuPree, Kelly J. ;

Darbonne, Walter C. ;

Ahn, Christina P. ;

Scales, Suzie J. ;

de Sauvage, Frederic J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (11) :4254-4259

[89] A Notch updated [J].

Tien, An-Chi ;

Rajan, Akhila ;

Bellen, Hugo J. .

JOURNAL OF CELL BIOLOGY, 2009, 184 (05) :621-629

[90] Endosomal entry regulates Notch receptor activation in Drosophila melanogaster [J].

Vaccari, Thomas ;

Lu, Han ;

Kanwar, Ritu ;

Fortin, Mark E. ;

Bilder, David .

JOURNAL OF CELL BIOLOGY, 2008, 180 (04) :755-762

← 1 2 3 4 5 6 7 8 9 10 →