Investigating mechanisms behind treatment response and resistance to PSMA-targeted radioligand therapy in prostate cancer

Recent advancements in the field of nuclear medicine have introduced promising theranostic agents for the treatment of advanced prostate cancer. Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), which delivers radiation to PSMA-expressing tumour cells, has been tremendously successful in a subset of patients. However, 30% of patients do not respond and all patients inevitably experience disease progression. Currently, clinicians are unable to predict which patients will fail treatment, nor do they know how to improve treatment durability. This project will use patient-derived models of prostate cancer to explore mechanisms of response and resistance to PSMA RLT. These models mimic PSMA expression and tumour heterogeneity seen in the clinic, enabling interrogation of the biological features that contribute to treatment response. We will investigate genetic and non-genetic tumour characteristics that may contribute to variable clinical outcomes, including tumour microenvironment, PSMA expression heterogeneity and molecular profiles. Students will gain expertise in cancer biology, tumour pathology and preclinical studies using patient-derived models, such as xenografts and organoids. Techniques may include biomedical imaging, immunohistochemistry, flow cytometry and bioinformatics. This work will be performed in collaboration with scientists, clinicians and patient advocates.