Assessing apoptotic and therapeutic properties of histone deacytelase inhibitors in mouse cancer models (LYMPHOMA)

Lymphoma represents one of the major forms of blood cancers faced by today's society and represents approximately 55% of new cancer cases. My research, being undertaken at the Peter MacCallum Cancer Centre, involves the investigation of a new form a chemotherapies known as histone deacetylase inhibitors (HDACi), which have shown great promise in treating lymphomas in the both the laboratory and clinic. While HDACi show great promise in treating lymphoma, little is known how these drugs actually work against cancer cells. HDACi have the ability to induce cell cycle arrest, differentiation and apoptosis in a variety of cancers. It is the main aim of my research to better understand the molecular pathways required by HDACi to induce their effects by using a mouse model that resembles human Burkitts lymphoma. To date I have shown that HDACi are able kill these lymphomas. To add to this story we have also deleted or over expressed important genes required by these lymphomas that enable survival and/or chemo-resistance and HDACi have been able to kill these lymphomas or inhibit their growth. Successful therapy experiments have also been achieved in mice bearing the same lymphomas, significantly extending the life of the mice. One of the HDACi I am investigating is being used in a phase I clinical trial with patients suffering from cutaneous T cell lymphoma (CTCL). Thus far patients have responded well to HDACi therapy and preliminary data suggests that there is significant alteration in the expression of certain genes of these patients to suggest this could be the primary reason for the patient's response. These and future results will allow a better understanding of how HDACi kill tumor cells and will allow us to devise new methods of treatment using