Signal Transducer and Activator of Transcription 3 Signaling Pathway: A Potential Target in Sarcoma Treatment

Michiro      Susa; Francis      J. Hornicek; Xianzhe      Liu; Zhenfeng      Duan

Abstract

Improvements in surgical technique, chemotherapy, and radiation have improved the prognosis of sarcoma patients, but it has since plateaued in recent years. Novel approaches are desperately needed for improved prognosis in the remaining patients. Targeting underlying molecular events have provided striking effects in some sarcomas. Signal transducers and activators of transcription 3 (STAT3) is a member of transcription factors that are activated by phosphorylation in the cytoplasm which are then translocated to the nucleus to regulate various gene expressions. STAT3 has been reported to be constitutively phosphorylated in various human cancers and has been cited as one of the instigators of neoplastic transformation. STAT3 and its associated signaling systems have been linked with resistance to chemotherapy and apoptosis suppression. These findings implicate to the possibility of targeting STAT3 for therapeutic intervention. This review provides an overview of STAT3 as a potential therapeutic target in the treatment of sarcoma.

Keywords: STAT3, sarcoma, cytokine, tyrosine kinase, small molecule inhibitors, chemotherapy, sarcoma patients, transcription 3 (STAT3), malignancies, pathogenesis, antisarcoma therapy, interleukin-6 (IL-6), epidermal growth factor (EGF), Src homology (SH2), phosphor-tyrosine (pTyr), tyrosine phosphorylation, homodimerizes, transcription factors, serine kinases, histone acetyl transferases, glucocorticoid receptor, Oncogenesis, Immune Evasion, multiple myeloma (MM), granular lymphocyte leukemia, nonsmall cell lung cancer, cell proliferation, angiogenesis, glioma, Inhibitors of Apoptosis (IAP), hematopoietic malignancies, hypoxiainducible factor 1-alpha (HIF-1a), immunosuppressive, dendritic cell, osteosarcoma, rhabdomyosarcoma, liposarcoma, chondrosarcoma, leiomyosarcoma, fibrosarcoma, xenotransplants, chemotherapeutics, Immunohistochemical, chordoma, cytokines, tumorigenesis, apoptosis, hematologic tumors, prostate cancer cells, isoenzyme, antiapoptotic proteins, plant polyphenols, curcumin, resveratrol, curcurbitacin, indirubin, flavoritidol, magnolol, cytochrome, bortezomib, multimodal, paclitaxel