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. 2023 Jul 11;4:1180869. doi: 10.3389/froh.2023.1180869

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© 2023 Sharon, Daher-Ghanem, Zaid, Gough and Kravchenko-Balasha.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Signaling pathways in HNSCC involved in the development of resistance to radiotherapy. The Epidermal Growth Factor Receptor (EGFR) was found as one of the central components of resistance to RT due to activation of pro-survival mechanisms, such as pAkt/MAPK or DNA repair pathways. However, combined inhibition of EGFR with RT did not improve HNSCC response to RT. This is due to alternative pathways activated in response to EGFR inhibition, such as HGF/MET, JAK-STAT, and Hedgehog pathways. Inhibition of these pathways, along with EGFR, improved the response of HNSCC to RT in preclinical studies.