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'Game changer' paediatric neuroblastoma drug trial announced

Tuesday October 6th 2020

A recently developed drug could be a “game changer” treatment for children with neuroblastoma, it was announced today.

Writing in The Journal of Clinical Investigation, Cancer Research UK-funded scientists say that they hope to begin a clinical trial, using fadraciclib to treat youngsters affected by the hard-to-treat disease, by the end of the year.

The drug was first unveiled in July and identified as likely to treat leukaemia, breast cancer and a range of other cancers.

Paediatric cancer researchers have been trying to find drugs that target genes that make the tumour more aggressive and enable it to grow faster -and have seized on the prospects of fadraciclib.

It is known that changes in the N-Myc gene occur in aggressive forms of neuroblastoma and while it is thought N-Myc may be a good target for treatment, the structure of the protein means it is extremely challenging to target treatment.

Now, scientists at The Institute of Cancer Research, London, UK, have found an indirect way to target N-Myc, giving them hope that it will be a game-changer for children with aggressive neuroblastoma.

Professor Louis Chesler and his team worked with international collaborators at the Baylor College of Medicine, Houston, USA, and found that fadraciclib can block N-Myc activity.

They tested the effectiveness of fadraciclib in the lab before testing it in mice and found that the drug slowed down and stabilised tumour growth. The mice who received it also survived for longer after treatment than untreated mice – in some cases more than twice as long.

They then went on to see how effective in mice fadraciclib was when used with temozolomide, a chemotherapy drug commonly used to treat children with neuroblastoma who relapse and found that each drug helped slow tumour growth when given separately. When they were given together, however, the drugs almost eradicated the tumours.

Lead author Professor Louis Chesler, professor of paediatric cancer biology at The Institute of Cancer Research, London, said: “Our study opens up the potential to treat children with aggressive cancers, such as neuroblastoma, with a class of precisely targeted cancer medicines that may be smarter and kinder. Children with cancer have not yet benefited enough from these medicines, which have reached adults with many kinds of cancer.

“It’s very important that we now focus on expanding the use of precision medicines in children’s cancers, guided by very detailed knowledge about their unique genetic makeup. This is what we are aiming to do with fadraciclib.

“It’s incredibly exciting to see this first drug head towards clinical trials, and I am very hopeful that it will prove as effective in patients as it has in the lab. We are also working on other drugs that could potentially block N-Myc in future.”

Co-author Professor Paul Workman, chief executive of The Institute of Cancer Research, London, added: “Our new results are very encouraging and could represent a huge step in advancing the treatment options available for children with cancer.

“Targeting N-Myc with a drug was thought to be an almost impossible task because of how challenging the N-Myc protein structure is to drug directly – so it’s very exciting to see fadraciclib showing promise by switching off the production of N-Myc.

Poon E et al. Pharmacological blockade of high-risk MYCN-driven neuroblastoma using an orally-bioavailable 1 CDK9/2 inhibitor. J Clin Invest 6 October 2020; doi: 10.1172/JCI134132

Tags: Cancer | Child Health | Pharmaceuticals | UK News

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