Blood ‘hot study’ shows potential for leukaemia drug
September 26, 2016
A ‘breakthrough’ adult leukaemia therapy called venetoclax could successfully target high-risk leukaemia subtypes in infants or children reveals an Australian study published this month, Childhood Cancer Awareness Month, in prestigious US haematology journal Blood.
The study’s lead authors are Professor Richard Lock, Head of Leukaemia Biology at Children’s Cancer Institute and Walter and Eliza Hall Institute’s Professor David Huang.
The team led by Professor Huang last month won a 2016 Australian Museum Eureka Prize awarded for their work on targeting the cell-survival protein BCL-2 with the drug venetoclax. Their recently published Blood paper was selected for a snapshot of ‘the hottest studies’ from each week’s issue, hand-picked by the journal’s editors.
Venetoclax has generated a lot of interest from cancer researchers based on a discovery at Melbourne’s Walter and Eliza Hall Institute made in the 1980s. This year it showed remarkable results in clinical trials for adults with chronic lymphocytic leukaemia (CLL). Most patients with an advanced form of CLL achieved either a partial or complete response. The drug’s target, BCL-2, is a cell survival protein and the product of an oncogene, a cancer-causing gene. After the success of the drug trials in adults, a next step was to test its effectiveness against children’s leukaemia.
The Blood study was a collaborative project with the Walter and Eliza Hall Institute, building on their many years’ of research into drugs like venetoclax and their mechanism of action. Testing on children’s cancers was done at Children’s Cancer Institute.
Professor Lock’s laboratory at Children’s Cancer Institute is the leukaemia testing site for the Pediatric Preclinical Testing Consortium, which is supported by the US National Cancer Institute. The site generates high-quality preclinical data to prioritise therapies using a successful model developed here by Professor Lock and his team. Several drugs we have prioritised have now been accelerated into clinical trials for children with leukaemia.
While leukaemia is the most common childhood cancer and has survival rates of around 90%, some leukaemia subtypes have much lower survival rates. Professor Richard Lock, Head of Leukaemia Biology at Children’s Cancer Institute, said that although it is disappointing that venetoclax is not looking as broadly active for the most common paediatric leukaemia (acute lymphocytic leukaemia or ALL) as it is in adult CLL, the research identified paediatric ALL sub-types that could be more susceptible to the drug than others and these are ‘high-risk’ sub-types.
With further testing, the drug could be used for targeted treatment for children and infants with these hardest-to-treat leukaemia sub-types as part of a personalised medicine approach. Data from the published study will be used to support a future clinical trial.
Professor Lock said venetoclax is likely to be most effective when used in combinations with other drugs and that further research is needed to determine which combinations work best.
Paper: ‘Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia’ http://www.bloodjournal.org/content/128/10/1382 with commentary on the paper at http://www.bloodjournal.org/content/128/10/1316
About Children’s Cancer Institute
Originally founded by two fathers of children with cancer in 1976, Children’s Cancer Institute is the only independent medical research institute in Australia wholly dedicated to research into the causes, prevention and cure of childhood cancer. Forty years on, our vision remains unchanged – to save the lives of all children with cancer and to eliminate their suffering. The Institute has grown to now employ more than 220 researchers, operational staff and students, and has established a national and international reputation for scientific excellence.
Our focus is on translational research, and we have an integrated team of laboratory researchers and clinician scientists who work together in partnership to discover new treatments which can be progressed from the lab bench to the beds of children on wards in our hospitals as quickly as possible. These new treatments are specifically targeting childhood cancers, so we can develop safer and more effective drugs and drug combinations that will minimise side-effects and ultimately give children with cancer the best chance of a cure with the highest possible quality of life.
We are currently leading the establishment of the Zero Childhood Cancer national child cancer personalised medicine program for children with the most aggressive cancers, in partnership with the Sydney Children’s Hospitals Network. This program will revolutionise the way treatment decisions are made, with the aim of improving survivorship for those children at highest risk of treatment failure from their disease.