Role of XIAP in Endocrine Cancer (Ovarian and Thyroid)

The X-linked inhibitor of apoptosis protein (XIAP) is a potent endogenous suppressor of apoptosis that promotes cancer cell survival by blocking caspase activation and cell death pathways. Due to its elevated expression in a range of human cancers and its important role in treatment resistance, XIAP has emerged as an attractive therapeutic target, with several small-molecule inhibitors currently in preclinical and clinical development. Our laboratory has a longstanding interest in the role of XIAP in endocrine-related cancers, particularly ovarian granulosa cell tumours and thyroid cancer. Using innovative in vitro models, genomic and transcriptomic approaches, and high-throughput drug screening platforms, we have identified a number of drug classes and signalling pathways that may act synergistically when combined with XIAP inhibition. These include pathways linked to nuclear receptor signalling, stress and survival responses, and oncogenic drivers that may be exploited therapeutically. Projects in this area will explore the biological function of XIAP in endocrine cancers and evaluate novel combination treatment strategies using advanced cell models and functional assays. The overall aim is to generate strong preclinical evidence for new therapeutic approaches that may ultimately improve outcomes for patients with these difficult-to-treat cancers.