Targeting the early steps of prostate cancer

Prostate cancer is the second most common cause of cancer related deaths in men. Loss of polarity and tissue architecture is a hallmark of epithelial cancer progression and leads to microenvironment alterations critical for tumour evolution and invasion. The importance of tissue architecture in Prostate Cancer prognosis is well recognized, however how it is controlled molecularly is poorly understood. Recent work by our laboratory has shown that key cell polarity regulator proteins are indispensable for prostate tissue homeostasis, and can contribute to prostate cancer initiation and progression.

This project investigates the molecular mechanisms by which the cell polarity network exerts a tumour suppressive function in the prostate epithelium, and assess how loss of cell polarity contributes to the initiation and progression of human prostate cancer. In particular, you shall delineate the molecular events that underpin the early steps of prostate cancer where tissue first become disorganised.  Ultimately, your work will determine the potential benefit of targeting the cell polarity signalling preventatively to “reorganize” abnormal pre-cancerous prostate tissue and stop its growth, thus providing an urgently needed novel route of therapeutic intervention. This project incorporates a variety of fundamental laboratory techniques, including mouse genetics, immunohistochemistry, confocal microscopy, 3D organoid prostate culture models (pictured), Patient Derived Xenografts (PDXs), RNAi and CRISPR technology.

In collaboration with Professor Declan Murphy, Peter MacCallum Cancer Centre