PARP Inhibitors – Useful in Treating Children With High-risk Neuroblastoma

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PARP inhibitor is a type of drug which is already used for the treatment of breast and ovarian cancer. It has also been shown to be useful in the treatment of children with high-risk neuroblastoma, a common childhood tumour with low rate of survival.

Neuroblastoma, a cancer in children arises from nerve cells in either the abdomen or chest. In some cases of neuroblastoma there is an abnormal gene called MYCN which makes it particularly difficult to treat. Treatment includes surgery, radiotherapy and chemotherapy, however, despite it, half of the children with high-risk neuroblastoma make it through.

Researchers at Sheffield University and The Institute of Cancer Research, London collaborated to conduct research to find a less toxic and more effective way to target high-risk neuroblastoma with increased levels of MYCN.

MYCN is how tumour cells grow, making them more dependant on PARP, a protein, for survival. The tumour cells are particularly killed by a drug that stops PARP working. An advantage of this therapy is that it does not harm normal non-tumour cells, a side effect that is often seen with chemotherapy.

The study was led by Dr Helen Bryant and David King in Sheffield, funded by cancer research charity Children with Cancer UK, in collaboration with Professor Louis Chesler at The Institute of Cancer Research (ICR).

The study found that the use of PARP inhibitors alongside chemotherapy and alone is an effective way of killing neuroblastoma cells.

Dr David King, children’s doctor at Sheffield Children’s NHS Foundation Trust and Children with Cancer UK researcher, said:

“Children with neuroblastoma and MYCN currently receive some of the most intense treatment used for any type of cancer. The harsh treatment causes numerous side effects and children often have long hospital stays. And despite the treatment, only about half of children with high-risk neuroblastoma will survive. PARP inhibitors are known to have very few side effects in adults and we have shown they may be an effective treatment for neuroblastoma. Their use in neuroblastoma could mean more children survive the disease and need less toxic treatment.

“We have shown that PARP inhibitors kill neuroblastoma cells with MYCN in the laboratory. The next step is to see whether they are beneficial in children with neuroblastoma, probably in combination with chemotherapy or radiotherapy. This would be done in a clinical trial.”


Dr Helen Bryant, research group lead and senior lecturer at Sheffield University, said:

“Our study has examined the way DNA is damaged and repaired – one of the features common in all cancers is that there are changes in that process. We were interested in how that process changes in neuroblastoma and whether we can exploit those changes to specifically kill cancer cells and leave the normal cells around the tumour unharmed. In this way we hope to develop kinder and less toxic therapies for children”.

“PARP inhibitors are being used successfully in women with breast and ovarian cancer so we are optimistic that this can be translated fairly quickly into children with neuroblastoma.”

Mark Brider, Chief Executive Officer, Children with Cancer UK, said:

“Neuroblastoma is one of the most common childhood tumours with around 100 children, mostly under five years old, diagnosed every year in the UK. Yet it also has one of the lowest survival rates – in its high-risk form the survival rate is sadly around just 50%. It remains one of the most difficult childhood cancers to cure”. 

“It is crucial that we find more effective and personalised treatments for children with neuroblastoma. The findings of Dr Bryant, Dr King and the teams in Sheffield and London represent an important step towards the development of new and kinder treatments that reduce the burden of toxicity for young cancer patients and improve survival rates in this aggressive and hard-to-treat cancer.” 

References

Reference: King, et al. (2020). MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma. Oncotarget. DOI: https://doi.org/10.18632/oncotarget.27329

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Dr. Aiman Shahab is a dentist with a bachelor’s degree from Dow University of Health Sciences. She is an experienced freelance writer with a demonstrated history of working in the health industry. Skilled in general dentistry, she is currently working as an associate dentist at a private dental clinic in Karachi, freelance content writer and as a part time science instructor with Little Medical School. She has also been an ambassador for PDC in the past from the year 2016 – 2018, and her responsibilities included acting as a representative and volunteer for PDC with an intention to make the dental community of Pakistan more connected and to work for benefiting the underprivileged. When she’s not working, you’ll either find her reading or aimlessly walking around for the sake of exploring. Her future plans include getting a master’s degree in maxillofacial and oral surgery, settled in a metropolitan city of North America.

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