Kimberley Clark

1. 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 PCa.

2. Investigating a role for NF-KB inhibition in overcoming therapeutic resistance to EGFR TKIs in lung cancer: Lung cancer is the leading cause of cancer deaths worldwide. Mutations in the epidermal growth factor receptor (EGFR) gene are one of the most commonly observed mutations in patients with non-small cell lung cancer (NSCLC). Multiple generations of EGFR tyrosine kinase inhibitors (TKIs) have provided significant benefit to clinical outcomes of patients with NSCLC, however resistance and/or disease recurrence almost always occurs. 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.