STAT3 transcription factor as target for anti-cancer therapy
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REVIEW
STAT3 transcription factor as target for anti‑cancer therapy Aliaa M. Mohassab1 · Heba A. Hassan1 · Dalia Abdelhamid1 · Mohamed Abdel‑Aziz1 Received: 21 June 2020 / Revised: 23 August 2020 / Accepted: 25 August 2020 © Maj Institute of Pharmacology Polish Academy of Sciences 2020
Abstract STATs constitute a large family of transcription activators and transducers of signals that have an important role in many cell functions as regulation of proliferation and differentiation of the cell also regulation of apoptosis and angiogenesis. STAT3 as a member of that family, recently was discovered to have a vital role in progression of different types of cancers. The activation of STAT3 was observed to regulate multiple gene functions during cancer-like cell proliferation, differentiation, apoptosis, metastasis, inflammation, immunity, cell survival, and angiogenesis. The inhibition of STAT3 activation has been an important target for cancer therapy. Inhibitors of STAT3 have been used for a long time for treatment of many types of cancers like leukemia, melanoma, colon, and renal cancer. In this review article, we summarize and discuss different drugs inhibiting the action of STAT3 and used in treatment of different types of cancer. Graphic abstract
Keywords Cancer · STAT3 · Melanoma · Leukemia
Introduction
* Heba A. Hassan [email protected] 1
Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
Signal transduction activator of transcription 3 (STAT3) is one of seven-membered protein family called STATs; (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6) [1]. It is responsible for transduction of both intracellular and extracellular signals to the nucleus as well as regulating gene expression of various physiological processes [2]. STAT3 plays a pivotal role among all STAT
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proteins and it has become the research focus as a potential target for treatment of cancer [3], as it censoriously regulates the transcription of multiple key genes involved in cell proliferation, differentiation, apoptosis, metastasis, inflammation, immunity, cell survival, and angiogenesis [4–6]. Also, several studies have reported that STAT3 has a crucial role in many diseases, such as stroke [7], myocardial ischemic injury [8], and obesity [9]. Nowadays, as researchers give great attention to cerebro- and cardiovascular diseases, STAT3 has been assumed to play essential roles in heart failure, hypertrophy, and arteriosclerosis [10–12]. STAT family was first discovered in 1988 as proteins bound to interferon (IFN)-stimulated response elements of DNA sequences to stimulate the transcription of type 1 IFNs [13]. Afterwards, in 1992, JAKs were discovered by three different laboratories and then JAK–STAT signaling pathway was established [14]. The word JAK comes from the name of a Roman two-faced god that implies two domains, a catalytic domain and a kinase-like domain [15]. JAK–STAT pathway is crucial for various homeostatic processes, such as hematopoiesis, ma
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