|Title:||Activation of STAT3 and STAT5 signaling in epithelial ovarian cancer progression: Mechanism and therapeutic opportunity||Authors:||CHIN-JUI WU
RUBY YUN-JU HUANG
|Issue Date:||2020||Journal Volume:||12||Journal Issue:||1||Source:||Cancers||Abstract:||
Epithelial ovarian cancer (EOC) is the most lethal of all gynecologic malignancies. Despite advances in surgical and chemotherapeutic options, most patients with advanced EOC have a relapse within three years of diagnosis. Unfortunately, recurrent disease is generally not curable. Recent advances in maintenance therapy with anti-angiogenic agents or Poly ADP-ribose polymerase (PARP) inhibitors provided a substantial benefit concerning progression-free survival among certain women with advanced EOC. However, effective treatment options remain limited in most recurrent cases. Therefore, validated novel molecular therapeutic targets remain urgently needed in the management of EOC. Signal transducer and activator of transcription-3 (STAT3) and STAT5 are aberrantly activated through tyrosine phosphorylation in a wide variety of cancer types, including EOC. Extrinsic tumor microenvironmental factors in EOC, such as inflammatory cytokines, growth factors, hormones, and oxidative stress, can activate STAT3 and STAT5 through different mechanisms. Persistently activated STAT3 and, to some extent, STAT5 increase EOC tumor cell proliferation, survival, self-renewal, angiogenesis, metastasis, and chemoresistance while suppressing anti-tumor immunity. By doing so, the STAT3 and STAT5 activation in EOC controls properties of both tumor cells and their microenvironment, driving multiple distinct functions during EOC progression. Clinically, increasing evidence indicates that the activation of the STAT3/STAT5 pathway has significant correlation with reduced survival of recurrent EOC, suggesting the importance of STAT3/STAT5 as potential therapeutic targets for cancer therapy. This review summarizes the distinct role of STAT3 and STAT5 activities in the progression of EOC and discusses the emerging therapies specifically targeting STAT3 and STAT5 signaling in this disease setting. ? 2019 by the authors. Licensee MDPI, Basel, Switzerland.
|DOI:||10.3390/cancers12010024||SDG/Keyword:||alpha smooth muscle actin; CD97 antigen; epidermal growth factor; granulocyte colony stimulating factor; histone H3; hypoxia inducible factor 1alpha; immunoglobulin enhancer binding protein; interleukin 11; interleukin 1beta; interleukin 23; interleukin 6; Janus kinase; leukemia inhibitory factor; leukotriene B4 receptor; microRNA; microRNA 551b; programmed death 1 ligand 1; programmed death 1 receptor; prolactin; protein p53; protein tyrosine kinase; reactive oxygen metabolite; STAT3 protein; STAT5 protein; transcription factor EZH2; transcription factor FOXP3; unclassified drug; unindexed drug; vasculotropin; vasculotropin receptor; vimentin; adaptive immunity; apoptosis; cancer associated fibroblast; cancer growth; carcinogenesis; CD4+ CD25+ T lymphocyte; CD4+ T lymphocyte; CD8+ T lymphocyte; disease association; gene activation; lipid metabolism; metastasis; ovary carcinoma; protein DNA binding; protein expression; protein phosphorylation; protein targeting; receptor binding; regulatory mechanism; regulatory T lymphocyte; Review; signal transduction; stroma cell; Th17 cell; tumor associated leukocyte; tumor growth; tumor microenvironment; tumor vascularization
|Appears in Collections:||醫學系|
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