THE ROLE OF AUTOPHAGY IN OROPHARYNGEAL AND ORAL CAVITY SQUAMOUS CELL CARCINOMA

Abstract

Autophagy is a mechanism involved in the elimination of damaged cellular components through lysosomal degradation and is capable of inducing programmed cell death. This process has recently gained much interest in cancer therapy due to its role in both pro- and anti-cancer activity. Oropharyngeal and oral cavity squamous cell carcinoma arise from the mucosa of the head and neck region. Despite their regional and histological similarities, these cancers suggested to have distinctive biological differences. This thesis investigated the role of autophagy in oropharyngeal and oral cavity squamous cell carcinoma through biological and translational research approaches. Specifically, this involved correlative ultrastructural studies using nanoparticles, live-cell imaging in-vitro studies and prognostic biomarker studies in a patient cohort from Southwest Sydney. In conclusion, this thesis had successfully established a correlative nanoparticle based immunolabelling method that improves autophagy assessment at the ultrastructural level, demonstrated that autophagy may play a protective role in squamous cell carcinoma after radiotherapy. Furthermore, the prognostic value of various autophagy biomarkers appeared to be variable between oropharyngeal and oral cavity squamous cell carcinoma, all of which supported the view that these cancers are biologically different.