From Experimental Models to Targeted Therapies for Oral Squamous Cell Carcinoma

Abstract

Cancer remains a leading cause of death worldwide, with OSCC being one of the most aggressive forms of HNC. OSCC often develops unnoticed until advanced stages, making treatment challenging and survival rates low. Standard therapies, including surgery, chemotherapy, radiotherapy and immunotherapy, can be effective but frequently result in significant side effects and high recurrence rates. There is a critical need for better preclinical models and innovative treatments to improve patient outcomes. This thesis focuses on optimizing preclinical models for OSCC research and emphasizes the need for better platforms to test new therapies. A key objective was to refine and evaluate the 4NQO-induced OSCC rat model, which closely replicates human OSCC progression. Two methods of 4NQO administration (via drinking water and topical application) were compared. The study found that the drinking water method more effectively induced tumors that mirrored human OSCC in terms of histopathology and progression, making it a superior approach for future OSCC research. Given the limitations of current OSCC treatments, the thesis also explored emerging therapeutic approaches, including plasma-treated PBS and suicide gene therapy using DPSC. Plasma-treated PBS was investigated for its ability to selectively kill cancer cells through oxidative stress while sparing healthy tissue, offering a non-invasive potential therapy. The HSV1-TK/GCV study demonstrated that DPSC could serve as effective carriers for delivering suicide gene therapy, improving tumor targeting and reducing systemic toxicity. Furthermore, this gene therapy system was explored in multiple cancer models, underscoring its broader potential beyond OSCC. In conclusion, this research strengthens the 4NQO rat model as a valuable tool for studying OSCC and testing new treatments. Additionally, it highlights promising therapeutic innovations that could lead to more targeted, effective, and less invasive treatment options for OSCC and other malignancies, ultimately improving patient outcomes.