TARGETING THE PIK3 PATHWAY IN NON-SMALL CELL LUNG CANCER

Abstract

The phosphotidyl inositol (3) kinase (PI3K) pathway is a critical survival pathway that is subverted in many cancers, particularly those that are receptor tyrosine kinase driven. This thesis describes a multi-pronged approach to examine the relevance of this pathway in epidermal growth factor receptor mutation positive lung adenocarcinoma, the commonest subtype in Singapore. I used a combination of integrative genomics and other molecular assays to describe the prevalence of PI3K pathway alterations in our local population (Tan, IJC 2014). I further evaluated the role of PI3K inhibition in the clinic, gaining significant insights to the challenges in developing this class of compounds (Tan, ASCO Proceedings 2014), and generated a range of preclinical models to inform on the potential therapeutic niches. Finally, with expanding knowledge on intra-tumoral heterogeneity, I present the case for high precision genomic interrogation, in order to delineate mutational context to predict therapeutic vulnerabilities (Tan, WCLC 2015).