Snowdome-supported researchers at Peter MacCallum Cancer Centre have discovered how a form of leukaemia fights back against a ground-breaking treatment, providing vital new leads on how to outwit the deadly disease.
Acute Myeloid Leukaemia (AML) stem cells are particularly aggressive, insidious and nimble. Knowing how they respond when under attack enables researchers to devise interventions that can neutralise the source of resistance before it develops.
As part of the research – and for the first time – Peter Mac’s Cancer Epigenetics Laboratory team has been able to grow and maintain leukaemia stem cells in a laboratory dish, making it easier and faster to test new treatments with the potential to eradicate the disease.
Recently published in the premier scientific journal Nature, the research shows how leukaemia stem cells react to BET-inhibitors – a novel treatment which is the subject of a current international clinical trial active at Peter Mac. This promising treatment targets epigenetic mechanisms of disease to effectively “turn-off” cancerous genes in AML.
The research found that resistance develops when the cells adapt, increasing expression of proteins in the WNT/β-catenin pathway to circumvent the drug and reactivate key cancer driving genes through a previously under-recognised mechanism.
The double discovery will boost understanding of AML, which affects more than 900 Australians each year, and 300,000 globally, with five-year survival rates of just 25% according to lead investigator, Associate Professor Mark Dawson “Our clinical trial of BET-inhibitors is giving new hope to selected patients with aggressive forms of AML. However, the risk of resistance developing is common in any cancer treatment. Knowing precisely how that happens in advance puts us one step ahead in outmaneuvering the disease.
“Being able to grow and maintain leukaemia stem cells in vitro, also gives us unprecedented access and insight into how they work, so we can find new and better ways to target and destroy them. This advance in our understanding of leukaemia cells is opening the doors to new treatment approaches and AML is a leukaemia that has long needed a major breakthrough to improve the future for all patients.”
The findings build on over ten years of research and clinical work, commenced at the University of Cambridge by Assoc Professor Dawson, who is now a consultant haematologist and head of the Cancer Epigenetics Laboratory at Peter Mac. In 2011, Assoc Professor Dawson and the team in Cambridge were instrumental in the initial development of this class of epigenetic drugs called BED bromodomain inhibitors. These drugs alter the way DNA is packaged and deciphered ultimately resulting in the ‘switching off’ of cancer causing genes.
This therapeutic strategy is very effective in pre-clinical models of aggressive leukaemias and now Assoc Professor Dawson is leading a first-in-class international clinical trial of these drugs in Australia, with the goal of increasing survival rates and advancing cures for aggressive blood cancers over the longer term.
The Snowdome Foundation is very proud to support the work of Assoc Professor Dawson and the Cancer Epigenetics Laboratory.