Gene Regulation Projects

Gene Regulation Projects - Research at Peter Mac

Currently Available Research Projects

Multiple myeloma (MM) is an incurable disease and there is clearly an unmet medical need for new therapeutic options. The primary aims of this project are to utilize a novel mouse model of MM to assess the therapeutic effects of combining novel tumor cell-selective apoptosis-inducing small molecules and biological agents. We will additionally dissect the molecular and biological events that underpin the single agent and combination therapy effects. The agents under investigation are the histone deacetylase inhibitor (HDACi) vorinostat, the proteosome inhibitor bortezomib and activators of the TRAIL death receptor pathway. As single agents, these are either currently in use for the treatment of MM or are in clinical development. We and others have recently demonstrated that a combination of vorinostat and the agonistic anti-TRAIL receptor monoclonal antibody (mAb) MD5-1, or bortezomib and MD5-1 can cure mice bearing cancers that are resistant to either agent used as a monotherapy. Moreover, a combination of bortezomib and HDACi has been shown to synergistically kill a variety of tumor cell lines.

We hypothesise that novel anti-cancer agents such as vorinostat, bortezomib and activators of the TRAIL pathway used alone or more likely in combination will provide therapeutic benefit for patients with MM. In addition, we propose that a detailed understanding of the molecular mechanisms of action of novel anti-cancer agents will lead to the development of rational combination strategies that will provide significantly greater therapeutic benefit than single agent therapy.

For more information on this project, contact the project supervisor:

Associate Professor Ricky Johnstone

+61 (0)3 9656 1238

ricky.johnstone@petermac.org