Abstract
Oral cancer is one of the leading causes of cancer-related deaths, and it has become a matter of serious concern due to the alarming rise in its incidence rate worldwide. Despite recent advancements in oral cancer treatment strategies, there are no significant improvements in patient’s survival rate. Among the numerous cell signaling pathways involved in oral cancer development and progression, STAT3 is known to play a multifaceted oncogenic role in shaping the tumor pathophysiology. STAT3 hyperactivation in oral cancer contributes to survival, proliferation, invasion, epithelial to mesenchymal transition, metastasis, immunosuppression, chemoresistance, and poor prognosis. A plethora of pre-clinical and clinical studies have documented the role of STAT3 in the initiation and development of oral cancer and showed that STAT3 inhibition holds significant potential in the prevention and treatment of this cancer. However, to date, targeting STAT3 activation mainly involves inhibiting the upstream signaling molecules such as JAK and IL-6 receptors. The major challenge in targeting STAT3 lies in the complexity of its phosphorylation- and dimerization-independent functions, which are not affected by disrupting the upstream regulators. The present review delineates the significance of the STAT3 pathway in regulating various hallmarks of oral cancer. In addition, it highlights the STAT3 inhibitors identified to date through various preclinical and clinical studies that can be employed for the therapeutic intervention in oral cancer treatment.
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Change history
07 March 2023
A Correction to this paper has been published: https://doi.org/10.1007/s12272-023-01434-5
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Acknowledgements
This work was supported by Ministry of Education Tier 1 Grant [R-184-000-301-114] to GS. This work was supported by the grant RBMH/PNH/SB/12/2015-1438 awarded to Ajaikumar B. Kunnumakkara by Indian Council of Medical Research, Government of India. The author Elina Khatoon acknowledges DBT BioCARe Women scientist scheme for providing her with the fellowship. Mangala Hegde acknowledges Science and Engineering Board (SERB)-National Post-Doctoral Fellowship (N-PDF) (PDF/2021/004053) for the financial support. Aviral Kumar acknowledges Prime Minister’s Research Fellowship (PMRF) program, Ministry of Education (MOE), Govt. of India for providing him the fellowship. The figures were created in BioRender.com
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Khatoon, E., Hegde, M., Kumar, A. et al. The multifaceted role of STAT3 pathway and its implication as a potential therapeutic target in oral cancer. Arch. Pharm. Res. 45, 507–534 (2022). https://doi.org/10.1007/s12272-022-01398-y
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DOI: https://doi.org/10.1007/s12272-022-01398-y