Where does funding go?
Funds from our events and donations go to Children’s Cancer Institute Australia (CCI) and Cancer Council NSW for specific neuroblastoma research projects. We donate profits from events to these research projects.
To date over $1.437 million has been donated to Children’s Cancer Institute into finding new improved treatments for children with neuroblastoma and $161,591 has been donated to Cancer Council (NSW).
Children’s Cancer Institute, Randwick (specifically CBL137)
Our Run2Cure event has supported the research of the drug called CBL137 since 2014. Over the past 4 years the event has raised a total of $346,718 for this drug. CBL137 has been researched by CCI through groups led by Professors Michelle Haber, Murray Norris and Glenn Marshall. It appears to be promising at this stage: http://www.sbs.com.au/news/article/2015/11/05/experimental-drug-giving-hope-kids-cancer
CBL137 is a novel drug developed for adult cancer in USA. It had not been tested for childhood cancer until the Institute looked at its qualities to target neuroblastoma tumours; specifically, those types of neuroblastoma that are linked to the MYCN gene which produces a protein in high volumes that is proven to create the metabolic environment for this cancer to grow aggressively.
Early results in laboratory models show the effectiveness of CBL137 in reducing aggressive neuroblastoma tumours. Not only does this research indicate the drug is very effective at reducing the cancer when used in combination with chemotherapy, but also that CBL137 does so with few damaging side effects because it does not damage DNA. It is DNA damage that is responsible for these side effects and if CBL137 can mean the cancer can be treated with lower dosages of toxic chemotherapy then this will not only improve cure rates but also reduce long term damage to the children treated.
In 2014 the early results of this work were presented at the international ANR (Advances in Neuroblastoma Research) Conference in Cologne and were recognised as the best presentation of this conference.
In November 2015 the first paper explaining the results of CBL137 research were published in the international journal Science Translation Medicine. This also led to significant media interest and articles in print, on radio and TV including ABC and SBS.
Current status of CBL137 single agent clinical trials
At present CBL137 is in clinical trial for adults in USA and Russia, these trials will establish the optimal dosage required to kill the cancer without serious side effects to patients, currently the trials are continuing due to the success of the drug and the lack of side effects suffered. As soon as the adult clinical trial is completed the dosage for children will be established as 80% of that identified as optimal for adults.
The next phase of this project will be a clinical trial of CBL137 for children at leading children’s cancer centres in the United States and at Sydney Children’s Hospital, Randwick, conducted through the US-based Children’s Oncology Group (COG), the largest children’s cancer study group in the world. This is the first time that a COG trial of this sort would be made available to Australian children. The clinical trial in both countries will be run in the hospitals by Dr David Ziegler, a senior researcher at Children’s Cancer Institute and Head of Clinical trials at the Kids Cancer Centre, Sydney Children’s Hospital (Randwick).
Additional CBL137 research
There is additional research being conducted by CCI related to CBL137 which requires urgent funding. Funds from Run2Cure will help CCI focus on how CBL137 will work in combination with other targeted therapies. The aim is for it to be optimised to treat the cancer cells most effectively but with less damage to healthy cells. CCI has already identified an agent that looks promising in laboratory models combined with CBL137. This now needs to be tested further to understand how it is working, if there are bio-markers that indicate this combination should be effective in particular children and the procedures for monitoring the combination drug usage and effect. Funding for this type of pre-clinical research is essential as often other funding sources focus on capital equipment and infrastructure rather than the senior scientists required to complete this ground-breaking work.
Cancer Council NSW (specifically N-Myc)
Run2Cure also supported a project sponsored by Cancer Council NSW. The project was called “The critical role of the long intergenic noncoding RNA MALAT1 in Neuroblastoma” and it has been conducted by Dr Tao Liu of the Children’s Cancer Institute (UNSW).
Neuroblastoma is one of the most common early childhood tumours in Australia and accounts for 15% of all cancer deaths in children. Sadly, despite 20 years of dramatic improvements in cancer treatments, only around 4 in 10 children who get neuroblastoma will survive 5 years or more.
We know that the formation of new blood vessels is essential in transforming a benign tumour into an aggressive neuroblastoma that spreads. However, little is known about why neuroblastomas are able to grow these blood vessels. This research project set out to identify which genes help neuroblastomas to spread, and how these genes could be targeted by therapies.
A protein called N-Myc is often associated with neuroblastoma – in fact the majority of patients who die from the disease have high levels of this protein. So far, researchers haven’t been sure why there is this link between the N-Myc protein and cancer. This changed over the last year when Dr Liu discovered that N-Myc increases the activity of a gene known as MALAT1. This gene is linked to the formation of new blood vessels, so when this gene becomes more active, it helps neuroblastoma to spread. The research team have found that by blocking MALAT1, it is possible to reduce the development of new blood vessels and the spread of the neuroblastoma cells.
Thanks to this Cancer Council NSW research grant, the team has uncovered the possibility of using MALAT1 as a new and effective target for neuroblastoma treatment. This means there is an opportunity to create new drugs that directly inhibit the activity of MALAT1 to stop neuroblastomas from spreading.
Going forward, Dr Liu and his team will work on developing stable MALAT1-blocking compounds. If these blockers are successful in the lab, this could lay the foundation to start clinical trials testing this treatment with neuroblastoma patients.