1. LUNG CANCER

Turning cytostatic drugs to cytotoxic therapies in non-small cell lung cancer: Lung cancer is the leading cause of cancer deaths worldwide. Mutations in key oncogenes EGFR (Epidermal Growth Factor Receptor) and KRAS (Kirsten Rat Sarcoma viral oncogene homolog) are commonly observed in patients with non-small cell lung cancer (NSCLC). Targeted therapies against EGFR and KRAS have transformed the treatment landscape of NSCLC, however acquired resistance remains a key barrier to durable remission. Our research seeks to investigate the mechanisms that drive treatment resistance in NSCLC in the following projects: 

• Defining the role of oxidative stress and cell stress mechanisms in resistance to targeted therapy: In NSCLC, treatment-induced stress plays a significant role in the development of therapeutic resistance. Cancer cells inherently possess an innate imbalance in redox signalling which enables them to tolerate increased cellular stress. Our preliminary studies demonstrate that EGFR- and KRAS-targeted therapies further induce oxidative stress and activate a cascade of cell survival responses in tumour cells. The aim of this project is to define the oxidative stress response in lung cancer and identify the key drivers to target and overcome treatment resistance to oncogene-targeted therapies.
• Using computational modelling to decode the complexity of adaptive treatment resistance: The ability of some cancer cells to adapt rapidly and survive after therapy plays a key role in the development of resistance, this adaptive response is highly dynamic and remains poorly understood. Traditional laboratory methods struggle to capture these dynamic, interlinked processes, making it challenging to pinpoint the precise mechanisms that drive post-treatment cell survival and resistance. As a result, key therapeutic vulnerabilities remain undefined, and promising combination treatment strategies to overcome resistance may have been overlooked. This project will address these barriers by integrating cutting-edge computational network modelling with traditional laboratory techniques.
• Investigating a role for NF-KB inhibition in overcoming therapeutic resistance to EGFR TKIs in lung cancer: NF-KB signalling is known to be upregulated in EGFR TKI-resistant NSCLC, and preclinical studies have demonstrated that NF-KB inhibition may provide an additional survival benefit when combined with EGFR TKIs. The aim of this project is to identify the cellular mechanisms by which NF-KB upregulation occurs in EGFR-TKI resistance in NSCLC, and to investigate whether NFKB can be targeted in pre-clinical animal models of NSCLC to overcome this.

2. PROSTATE CANCER

Identification and validation of novel MYBL2 inhibitors for prostate cancer: MYBL2, a MYB family transcription factor, is a physiological regulator of cell cycle progression, cell survival and cell differentiation. MYBL2 is commonly amplified in aggressive castrate resistant disease. The aim of this project is to determine the mechanisms of MYBL2 upregulation in prostate cancer and its role in different disease stages. Secondly, this project aims to investigate and validate candidate compounds from a virtual screening platform as novel MYBL2 inhibitors that can be used in treatment of aggressive prostate cancer.