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Hope for non-toxic treatment for child cancer

Drug combination promising in treating neuroblastoma

Adrian O'Dowd

Friday, 16 November 2018

New hope in treating neuroblastoma – one of the most common childhood cancers – has been found by researchers investigating treatments for the condition in animals.

Australian researchers found a combination of two drugs made tumours disappear in mice, making it more effective than any other drugs tested in these animals.

Professor Murray Norris, deputy director of the Children's Cancer Institute Australia for Medical Research in Sydney, was due to tell the 30th EORTC [European Organisation for Research and Treatment of Cancer]-NCI [National Cancer Institute]-AACR [American Association for Cancer Research] Symposium on Molecular Targets and Cancer Therapeutics held in Dublin, Ireland, today, that the findings were highly significant.

Presenting details of his research* at the symposium, Professor Norris warned that it would be some time before the drug combination would be tested in children and, if successful, made available more widely to treat children with this disease, even though both drugs were currently undergoing clinical trial in a range of adult cancers.

Neuroblastoma, a common childhood cancer, is the leading single cause of cancer deaths in children aged under five. Despite using intensive treatment regimens, children with the most aggressive forms of neuroblastoma have a less than 50% survival rate.

CBL0137, which belongs to a new class of drugs called curaxins, attacks the structure of cancer cells, but is a safe drug that does not damage DNA in normal cells.

Professor Norris and colleagues used RNA sequencing technology that can detect drug-induced changes in tumours, to see how the combination of CBL0137 and panobinostat stopped neuroblastoma growing.

Professor Norris said: “We have found that when we combined CBL0137 and panobinostat to treat mice bearing neuroblastomas, the tumours disappeared and never came back during the entire experiment, whereas the tumours continued to grow in mice that received either no treatment or only single drug treatment.

“This is a highly significant finding as this drug combination is the most effective therapy that we have observed in this neuroblastoma mouse model. It is unusual to see this effect, especially in these mice where neuroblastoma develops within seven weeks of birth and is aggressive in nature.

“Our results suggest that these drugs work through two different mechanisms that offer a two-pronged attack. One of these mechanisms appears to be a direct attack on the cancer cells themselves, killing them by inhibiting DNA repair; then a second mechanism is involved in inducing a robust immune response. This is very exciting and will hopefully facilitate the clinical development of effective and non-toxic therapies for childhood cancer,” he said.

Further laboratory research by the team also showed that CBL0137 and panobinostat slowed the growth of aggressive leukaemias in mice and significantly extended survival.

A phase I clinical trial of CBL0137 in children with neuroblastoma and other difficult-to-treat childhood cancers is planned to start in 2019, following the completion of a phase I clinical trial of the drug in adults with solid cancers and previously treated blood cancers.

Co-chair of the Symposium, Dr James Gulley, director of the Medical Oncology Service at the NIH/NCI Center for Cancer Research in the USA, said: “Although these are results from work conducted in mice, they are very interesting and suggest the exciting possibility that this drug combination might work more effectively than single agents in children with this rare but aggressive tumour.”


*M, Norris. Chromatin destabilization by CBL0137 and panobinostat leads to complete tumour regression of childhood neuroblastoma in immunocompetent transgenic mice. Presented at the 30th European Organisation for Research and Treatment of Cancer-National Cancer Institute- American Association for Cancer Research Symposium on Molecular Targets and Cancer Therapeutics. 16 November 2018.

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