Li, YanSaad Ghafil AlRaheem, ZainabLe, Tao TSeyfoddin, Ali2025-07-232025-07-232025-07-23Current Issues in Molecular Biology, ISSN: 1467-3037 (Print); 1467-3045 (Online), MDPI AG. doi: 10.3390/cimb470805841467-30371467-3045http://hdl.handle.net/10292/19594Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have emerged as targeted therapies for OSCC in clinical trials. However, their clinical efficacy remains a challenge. Cannabidiol (CBD), a non-psychoactive phytochemical from cannabis, has demonstrated anticancer and immunomodulatory properties. CBD induces apoptosis and autophagy and modulates signaling pathways often dysregulated in HNSCC. This review summarizes the molecular mechanisms of EGFR-TKIs and CBD and their clinical insights and further discusses potential implications of combination targeted therapies.© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).https://creativecommons.org/licenses/by/4.0/1108 Medical MicrobiologyMicrobiology3107 Microbiologyhead and neck squamous cell carcinoma (HNSCC)epidermal growth factor receptor (EGFR)tyrosine kinase inhibitors (TKIs)cannabidiol (CBD)Journal ArticleOpenAccess10.3390/cimb47080584