Project 1 - CBL137 combination with other targeted therapies

The next research project focuses on how CBL137 will work in combination with other targeted therapies with the aim that it can be optimised by to treat the cancer cells most effectively but with less damage to healthy cells. Children's Cancer Institute has already identified an agent that looks promising in laboratory models combined with CBL137, now this 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.

CBL137 has been researched by CCI through groups led by Professors Michelle Haber, Murray Norris and Glenn Marshall.

“The support of Neuroblastoma Australia of our group over a decade, has been absolutely invaluable in helping us to understand new mechanisms underlying the growth and aggressive behaviour of neuroblastoma, and to develop new treatments to target these mechanisms which have translated to a number of completed, current and planned clinical trials. We are indebted to Neuroblastoma Australia for working with us so closely towards our common goal of one day making neuroblastoma a completely treatable and hopefully preventable disease.” - Professor Michelle Haber

Project 2 - Improved pre-clinical efficacy of CBL0137 by combination with HDAC inhibition

We are supporting a new project, which aims to improve pre-clinical efficacy of CBL0137 by combination with a TGA/FDA-approved drug, panobinostat.

Preliminary work in high-risk neuroblastoma mouse models from the Children’s Cancer Institute has shown that CBL0137/panobinostat combination markedly prolonged disease-free survival compared with either of these two drugs alone, or compared with conventional chemotherapy drugs for neuroblastoma.

The team will further test if CBL0137/panobinostat can sensitise relapsed/resistant PDX models to standard chemotherapy backbones that are often ineffective for these tumours. This study also aims to understand how CBL0137 and panobinostat interact to specifically target tumour cells. Understanding of the underlying mechanisms will help reveal potential drug targets and develop safe and highly efficacious treatments for high-risk neuroblastoma.

What is CBL137

CBL137 combination with other targeted therapies 

CBL137 is a novel drug developed for adult cancer in USA. It had not been tested for childhood cancer until the CCI 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.

The research project involved identifying whether this drug could be effective in treating high-risk neuroblastoma in laboratory models as a single agent, at the next stage this single agent will go to a phase one clinical trial to confirm the acceptable dosage of CBL137 to treat this aggressive cancer in children.

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