Recent Knowledge on Squamous Cell Carcinoma of the Oral Cavity: Contributing Factors, Underlying Molecular Pathways, and Current Attitudes in the Therapeutic Approaches



Anzabi RM ; Davodpour AH ; Ghodratizadeh S ; Nikeghbal D ; Sadeghzade A ; Mohammadikhah M ; Rostamzadeh S
Source: International Journal of Molecular and Cellular Medicine Published:2025

Abstract

Oral cavity squamous cell carcinoma (OCSCC) is a prevalent malignancy associated with considerable morbidity and mortality. This article offers a comprehensive overview of its major risk factors, molecular characteristics, and emerging therapeutic approaches. Key risk factors include tobacco use, alcohol consumption, and environmental exposures such as air pollution. Viral infections, particularly with Epstein–Barr Virus (EBV) and high-risk genotypes of Human Papillomaviruses (HPV), are also implicated in OCSCC pathogenesis. At the molecular level, OCSCC is characterized by aberrant expression of growth factors, especially transforming growth factor α (TGF-α) and epidermal growth factor receptor (EGFR). EGFR overexpression, often due to gene amplification, is closely associated with tumor progression and poor clinical outcomes. These insights into molecular pathways are guiding the development of targeted therapies. Innovative treatments are being explored, including combination therapies such as metformin with 4SC-202, which show promise in reducing tumor cell migration and enhancing chemotherapy sensitivity. Additionally, nanoengineered formulations of cisplatin aim to improve drug delivery specificity and minimize systemic toxicity, offering a more patient-friendly approach. The article emphasizes the need for continued investigation into novel therapeutic strategies and a deeper understanding of the molecular basis of OCSCC to improve treatment outcomes. Future research priorities include the identification of new risk factors, refinement of induction chemotherapy protocols, and incorporation of personalized treatment strategies. Addressing these areas is crucial for advancing prevention, enabling early diagnosis, and improving survival and quality of life for patients with OCSCC. This work supports ongoing progress in oral cancer research and clinical care. © 2025 Elsevier B.V., All rights reserved.