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        The multifaceted role of STAT3 pathway and its implication as a potential therapeutic target in oral cancer

        Elina Khatoon,Mangala Hegde,Aviral Kumar,Uzini Devi Daimary,Gautam Sethi,Anupam Bishyaee,Ajaikumar B. Kunnumakkara 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.8

        Oral cancer is one of the leading causes of cancer-related deaths, and it has become a matter of seriousconcern due to the alarming rise in its incidence rate worldwide. Despite recent advancements in oral cancer treatmentstrategies, there are no signifi cant improvements in patient’ssurvival rate. Among the numerous cell signaling pathwaysinvolved in oral cancer development and progression, STAT3is known to play a multifaceted oncogenic role in shapingthe tumor pathophysiology. STAT3 hyperactivation in oralcancer contributes to survival, proliferation, invasion, epithelialto mesenchymal transition, metastasis, immunosuppression,chemoresistance, and poor prognosis. A plethoraof pre-clinical and clinical studies have documented the roleof STAT3 in the initiation and development of oral cancer and showed that STAT3 inhibition holds signifi cant potentialin the prevention and treatment of this cancer. However, todate, targeting STAT3 activation mainly involves inhibitingthe upstream signaling molecules such as JAK and IL-6receptors. The major challenge in targeting STAT3 lies inthe complexity of its phosphorylation- and dimerizationindependentfunctions, which are not aff ected by disruptingthe upstream regulators. The present review delineates thesignifi cance of the STAT3 pathway in regulating varioushallmarks of oral cancer. In addition, it highlights the STAT3inhibitors identifi ed to date through various preclinical andclinical studies that can be employed for the therapeuticintervention in oral cancer treatment.

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