St Vincent's Institute

Anti-cancer and anti-metastasis drug development

In vitro and in vivo models are being used to assess drug efficacy for several promising anti-cancer and anti-metastasis agents. One belongs to a class of agents known as the matrix metalloproteinase inhibitors. Matrix metalloproteinases (MMPs) play a role in virtually all phases of tumour growth and metastasis and we are particularly excited by the prospect that this agent may be synergistic with current, conventional anti-cancer drugs.

This work is being conducted in collaboration with A/Prof Erik Thompson's VBRCR group. Another agent under investigation has putative growth factor inhibitory activity and has marked ability to inhibit bone damage associated with cancer metastasis. Microarray expression profiling technology is a component of our studies to explore the precise action of these agents. Gene expression profiling of the epithelial-to-mesenchymal transition in cancer metastasis

Genomic profiling of the epithelial-to-mesenchymal transition in cancer metastasis

During metastatic progression, a small population of cancer cells leave the primary tumour and disseminate to secondary organs. As part of this process, the gain of migratory and invasive properties for these cells is associated with loss of epithelial morphology and acquisition of mesenchymal characteristics. This process has been referred to as an epithelial to mesenchymal transition (EMT). Genomic profiling of in vitro models of the EMT are under investigation. While the established gene-fingerprint of the EMT is being refined for potential application in clinical diagnosis, the identification of functional drivers of the EMT process is being pursued to reveal potential drug targets of the metastatic cascade.

Gene expression changes associated with diabetic complications

We are identifying genes that are associated with diabetic kidney damage (nephropathy) in a rat model of the disease. Having completed the first phase of analysis our attention is now focused on twenty differentially expressed genes for animals progressing to disease. The next phase of this work will be to examine if these same genes are altered for human biopsy samples taken from patients with Type I diabetes.

In an associated study using cells taken from both rat and human kidneys and inducing diabetic conditions, one novel finding has been the dramatic increase in expression for one particular gene which appears to modulate oxidative stress response. In association with the Institute's Structural Biology Laboratory, we are perusing this gene as a potential new therapeutic target.

Cancer bioinformatics

An increasing number of mRNA expression databases are available which profile patient tumour specimens and cancer cell lines. For the latter, several are linked to drug activity/sensitivity patterns.

We are employing statistical and data visualization tools to mine these sites and identify gene-gene and gene-drug correlations that have an apparent associated role in the promotion or suppression of tumour growth and metastasis. A particular emphasis is placed on 'gene discovery' and identifying potential drugs to target a number of key events that take place during tumour progression.