Therapeutic inhibition of jak activity inhibits progression of gastrointestinal tumors in mice

Molecular Cancer Therapeutics

Volumn 13, Issue 2, 2014, Pages 468-474

  Stuart, Emma ^a,c   Buchert, Michael ^a,c   Putoczki, Tracy ^a,c   Thiem, Stefan ^a,c   Farid, Ryan ^a,c   Elzer, Joachim ^a   Huszar, Dennis ^c   Waring, Paul M ^b   Phesse, Toby J ^a,c   Ernst, Matthias ^a,d  

^a WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c LUDWIG INSTITUTE FOR CANCER RESEARCH   (Australia)

^d ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; CYCLINE; GLYCOPROTEIN GP 130; JANUS KINASE 1; JANUS KINASE 2; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE; STAT3 PROTEIN;

129 MOUSE; ANIMAL; ANTAGONISTS AND INHIBITORS; APOPTOSIS; C57BL MOUSE; CELL PROLIFERATION; COLONIC NEOPLASMS; DISEASE COURSE; DRUG EFFECTS; EPITHELIUM; GASTROINTESTINAL NEOPLASMS; GENE EXPRESSION; GENETICS; HUMAN; IMMUNOHISTOCHEMISTRY; KNOCKOUT MOUSE; METABOLISM; PATHOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSGENIC MOUSE; TUMOR VOLUME; WESTERN BLOTTING;

ANIMALS; APOPTOSIS; BLOTTING, WESTERN; CELL PROLIFERATION; COLONIC NEOPLASMS; CYTOKINE RECEPTOR GP130; DISEASE PROGRESSION; EPITHELIUM; GASTROINTESTINAL NEOPLASMS; GENE EXPRESSION; HUMANS; IMMUNOHISTOCHEMISTRY; JANUS KINASE 1; JANUS KINASE 2; MICE, 129 STRAIN; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; PROLIFERATING CELL NUCLEAR ANTIGEN; PYRAZOLES; PYRIMIDINES; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; STAT3 TRANSCRIPTION FACTOR; TUMOR BURDEN;

EID: 84894212213     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-13-0583-T     Document Type: Article

References (23)

1. Bromberg J. Stat proteins and oncogenesis. J Clin Invest 2002;109: 1139-42.
2. Jarnicki A, Putoczki T, Ernst M. Stat3: linking inflammation to epithelial cancer-more than a "gut" feeling? Cell Div 2010;5:14-28.
3. Bollrath J, Phesse TJ, von Burstin VA, Putoczki T, Bennecke M, Bateman T, et al. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 2009;15:91-102.
4. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003;374:1-20.
5. Haftchenary S, Avadisian M, Gunning PT. Inhibiting aberrant Stat3 function with molecular therapeutics: a progress report. Anticancer Drugs 2011;22:115-27.
6. Noor SM, Bell R, Ward AC. Shooting the messenger: targeting signal transduction pathways in leukemia and related disorders. Crit Rev Oncol Hematol 2011;78:33-44.
7. Hedvat M, Huszar D, Herrmann A, Gozgit JM, Schroeder A, Sheehy A, et al. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell 2009;16: 487-97.
8. Jenkins BJ, Grail D, Nheu T, Najdovska M, Wang B, Waring P, et al. Hyperactivation of Stat3 in gp130 mutant mice promotes gastric hyperproliferation and desensitizes TGF-beta signaling. Nat Med 2005;11:845-52.
9. Sorriano P. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 1999;21:70-71.
10. Alonzi T, Maritano D, Gorgoni B, Rizzuto G, Libert C, Poli V. Essential role of STAT3 in the control of the acute-phase response as revealed by inducible gene inactivation [correction of activation] in the liver. Mol Cell Biol 2001;21:1621-32.
11. Becker C, Fantini MC, Neurath MF. High resolution colonoscopy in live mice. Nat Protoc 2006;1:2900-04.
12. Thiem S, Pierce TP, Palmieri M, Putoczki TL, Buchert M, Preaudet A, et al. mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice. J Clin Invest 2013;123: 767-81.
13. Putoczki TL, Thiem S, Loving A, Busuttil RA, Wilson NJ, Ziegler PK, et al. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell 2013;24:257-71.
14. Johnstone CN, White SJ, Tebbutt NC, Clay FJ, Ernst M, Biggs WH, et al. Analysis of the regulation of the A33 antigen gene reveals intestine-specific mechanisms of gene expression. J Biol Chem 2002; 277:34531-39.
15. Judd LM, Alderman BM, Howlett M, Shulkes A, Dow C, Moverley J, et al. Gastric cancer development in mice lacking the SHP2 biding site on the IL-6 family co-receptor gp130. Gastroenterology 2004;126: 196-207.
16. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74.
17. Kim DY, Cha ST, Ahn DH, Kang HY, Kwon CI, Ko KH, et al. STAT3 expression in gastric cancer indicates a poor prognosis. J Gastroenterol Hepatol 2009;24:646-51.
18. Morikawa T, Baba Y, Yamauchi M, Kuchiba A, Nosho K, Shima K, et al. STAT3 expression, molecular features, inflammation patterns, and prognosis in a database of 724 colorectal cancers. Clin Cancer Res 2011;17:1452-62.
19. McFarland BC, MaJY, Langford CP, Gillespie GY, Yu H, Zheng Y, et al. Therapeutic potential of AZD1480 for the treatment of human glioblastoma. Mol Cancer Ther 2011;10:2384-93.
20. Couto JP, Almeida A, Daly L, Sobrinho-Simoes M, Bromberg JF, Soares P. AZD1480 blocks growth and tumorigenesis of RET-activated thyroid cancer cell lines. PLoS ONE 2012;7:e46869.
21. Scuto A, Krejci P, Popplewell L, Wu J, Wang Y, Kujawski M. The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival. Leukemia 2011;25:538-50.
22. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 2009;9:798-809.
23. Britschgi A, Andraos R, Brinkhaus H, Klebba I, Romanet V, Muller U, et al. JAK2/STAT5 inhibition circumvents resistance to PI3K/mTOR blockade: a rationale for cotargeting these pathways in metastatic breast cancer. Cancer Cell 2012;22:796-811.