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

• Published in: Molecular cancer therapeutics Vol. 13; no. 2; pp. 468 - 474
• Main Authors: Stuart, Emma, Buchert, Michael, Putoczki, Tracy, Thiem, Stefan, Farid, Ryan, Elzer, Joachim, Huszar, Dennis, Waring, Paul M, Phesse, Toby J, Ernst, Matthias
• Format: Journal Article
• Language: English
• Published: United States 01.02.2014
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - genetics; Blotting, Western; Cell Proliferation - drug effects; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - prevention & control; Cytokine Receptor gp130 - genetics; Cytokine Receptor gp130 - metabolism; Disease Progression; Epithelium - drug effects; Epithelium - metabolism; Epithelium - pathology; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - metabolism; Gastrointestinal Neoplasms - prevention & control; Gene Expression - drug effects; Humans; Immunohistochemistry; Janus Kinase 1 - antagonists & inhibitors; Janus Kinase 1 - metabolism; Janus Kinase 2 - antagonists & inhibitors; Janus Kinase 2 - metabolism; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Proliferating Cell Nuclear Antigen - metabolism; Pyrazoles - pharmacology; Pyrimidines - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Tumor Burden - drug effects; Tumor Burden - genetics

Aberrant activation of the latent transcription factor STAT3 and its downstream targets is a common feature of epithelial-derived human cancers, including those of the gastrointestinal tract. Mouse models of gastrointestinal malignancy implicate Stat3 as a key mediator of inflammatory-driven tumorig...