This project studies the anti-cancer activities of a new class of drugs known as histone deacetylase inhibitors (HDACi) with the aim of using them in a more rational way for the treatment of cancer. In addition, we will study the effects of HDACi in combination with other molecular therapeutics to enhance the potency of these drugs against otherwise non-responsive tumours.
We are interested in determining exactly how anti-cancer drugs kill tumor cells, and how these cells often overcome or circumvent the activity of these agents. The particular class of chemotherapeutic drugs that will be studied are called histone deacetylase inhibitors (HDACi) that have already shown promise in both laboratory experiments and in pre-clinical trials in patients.
Like many chemotherapeutic drugs, HDACi kill tumors cells through a cell suicide process called apoptosis. We now know a lot about apoptosis, and the important proteins and pathways necessary for cell suicide to occur have been well delineated. We have now established a mouse model of human lymphoma whereby particular pro-apoptotic proteins have been eliminated or anti-apoptotic proteins overexpressed.
Such abnormalities occur in human cancer and using this system, we will identify the apoptotic proteins and pathways that are necessary for different HDACi to kill cancer cells. Such information will lead to a more targeted or rational approach to chemotherapy where a specific anti-cancer drug will be used to treat a cancer that has defined genetic abnormalities that impinge on apoptosis.
Dr Ricky Johnstone
Peter MacCallum Cancer Centre
Research Grant: 2006-2008
$70,000 per annum