The JAK/STAT signaling cascade in gastric carcinoma (Review)

Khanna,Puja; Chua,Pei  Jou; Bay,Boon  Huat; Baeg,Gyeong  Hun

doi:10.3892/ijo.2015.3160

The JAK/STAT signaling cascade in gastric carcinoma (Review)

Authors:
- Puja Khanna
- Pei Jou Chua
- Boon Huat Bay
- Gyeong Hun Baeg
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Affiliations: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 597, Republic of Singapore
Published online on: September 14, 2015 https://doi.org/10.3892/ijo.2015.3160
Pages: 1617-1626

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Abstract

Gastric carcinoma remains one of the most prevalent forms of cancer worldwide, despite the decline in incidence rates, increased awareness of the disease and advancement in treatment strategies. Helicobacter pylori infection, dietary factors, lifestyle influences and various genetic aberrations have been shown to contribute to the development and progression of gastric cancer. Recent studies on the genomic landscape of gastric adenocarcinoma have identified several key signaling molecules, including epidermal growth factor receptor family (ErbB) members, vascular endothelial growth factor receptor family (VEGFR) members and PI3K/Akt/mTOR pathway components, that have been implicated in the molecular pathogenesis of gastric cancers. However, clinical trials with compounds that target these molecules have failed to show a significant improvement in overall survival rates when supplemented with conventional therapies. Therefore, it is essential to identify effective prognostic and/or diagnostic biomarkers and develop molecular targeted therapies. The JAK/STAT cascade is a principal signal transduction pathway in cytokine and growth factor signaling, regulating various cellular processes such as cell proliferation, differentiation, migration and survival. Numerous in vivo and in vitro studies have shown that dysregulated JAK/STAT signaling is a driving force in the pathogenesis of various solid cancers as well as hematopoietic malignancies. Hence, a large number of preclinical and clinical studies of drugs targeting this pathway are currently underway. Notably, aberrant JAK/STAT signaling has also been implicated in gastric cancers. In this review, we focus on the ongoing research on the JAK/STAT cascade in gastric carcinoma and discuss the therapeutic potential of targeting JAK/STAT signaling for the treatment of gastric cancer.

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