Dr Gemma Kelly, Dr Marco Herold, Dr MaryAnn Anderson
The Walter and Eliza Hall Institute of Medical Research
Leukaemia, lymphoma & myeloma
What is the project?
In previous work, we found the growth of some lymphomas driven by abnormal levels of a protein called MYC, depend on expression of the pro-survival protein MCL-1. This project will utilise sophisticated pre-clinical models of this lymphoma to investigate the therapeutic potential of a novel BH3-mimetic inhibitor. This research will help inform the care and prognosis of patients with MCL-1 dependent cancers.
What is the need?
Many cancer cells evade cell death which can result in uncontrolled growth of cells and resistance to treatment. A new class of cancer drugs, called BH3 mimetics, have recently been developed. These drugs directly trigger cell death in malignant cells by binding and blocking the action of certain cell survival proteins. The current lead BH3 mimetic drug is Venetoclax. Venetoclax was recently approved in several countries, including Australia, and it is transforming the prognosis for patients with refractory Chronic Lymphocytic Leukaemia. However, there is growing evidence that the sustained growth of some other cancers depends on a different pro-survival protein, MCL-1.
What are you trying to achieve?
There is evidence that there are a growing number of human cancers that depend on a pro-survival protein called MCL-1 for their continued growth. Therefore, we predict that blocking the MCL-1 protein would be an effective treatment option for these patients and lead to the death of the cancer cells. We have developed sophisticated pre-clinical models of lymphoma and leukaemia that we can use to test this hypothesis. Our experiments will determine the effectiveness of targeting MCL-1 to kill different blood cancers and also reveal the potential effect of the MCL-1 inhibition on the normal healthy cells and, in this way, anticipate any likely side effects. We hope that our research will support the clinical application of this class of drugs in patients in the future.
Cancer Council Victoria Research Grant