Ovarian Granulosa Cell Tumour Pathogenesis and Novel Therapeutic Targeting

Granulosa cell tumours (GCT) of the ovary are rare endocrine tumours that both produce and respond to hormones. Adult GCT are characterised by a near-universal mutation in the FOXL2 gene, which is believed to play a central role in tumour development. However, despite this hallmark mutation, the molecular mechanisms that drive tumour progression, recurrence, and treatment resistance remain poorly understood, and therapeutic options for advanced disease are limited. Our group is investigating the biology of GCT using a range of innovative approaches, including CRISPR-based functional studies, transcriptomic analyses, and high-throughput drug screening. These studies have identified a number of candidate genes and drug classes that show promise, particularly in combination with inhibition of X-linked inhibitor of apoptosis protein (XIAP), a key regulator of cell survival. Current projects are focused on understanding the molecular pathways that underpin these synergistic responses, with particular interest in hormone signalling and nuclear receptors, including pathways that may be therapeutically co-targeted. This project will suit students interested in cancer biology, endocrine signalling, functional genomics, and preclinical therapeutic development. There is scope for projects spanning tumour pathogenesis, mechanism of drug action, biomarker discovery, and novel combination therapies.