The goal of the Prostate Oncobiology group is to advance our understanding of cancer signalling pathways and to identify tumour-initiating cells. A central challenge in cancer research is the identification of cancer patients whose disease will eventually progress to the lethal stage. Due to the cytogenetic complexity of epithelial cancers, little is known about their origins and the steps required for progression from local to advanced disease.
The recent combination of pathological and morphological changes with whole-genome tools have characterised normal and cancer genomes, providing the means to highlight multiple somatic alterations that occurs in cancer, such as mutations in metabolic pathways. Our cancer profiling approach allows us to identify ETV1 as a key regulator of steroid and cholesterol biosynthesis pathways. We are characterising the contribution of ETV1 transcriptional program to cancer metabolism reprogramming, and how disruption of the selected pathway by gene targeting and drug treatment affects tumour growth and progression in vivo.
Growing evidence proposes that tumour initiation from distinct cell types in the lineage hierarchy gives rise to tumour subtypes with different prognoses and/or treatment responses. Thus, a key problem remains the identification of the cell type capable of initiating and sustaining growth of the tumour. Being able to target neoplastic cell populations based on unique surface-marker expression patterns has provided a new avenue in cancer research to study directly the cells thought to be at the root of the disease. To define the prostate cell populations that evolve to tumour-initiating cells, we are characterising the basal and luminal epithelial compartments by integrating single-cell profiling and functional analysis in normal and tumour mouse models.
Our research goals are directed toward identifying cells of origin of prostate cancer, and the pathways responsible for the transformation of normal target cells into self-renewing cancer cells to pursue the development of better and personalised therapeutics.