Revolutionary new bone cancer drug could save children's lives

A new drug that works against the main types of primary bone cancer has been developed by researchers at the University of East Anglia and University of Sheffield.

An illustration of an RNA molecule
  • Researchers at the University of Sheffield and University of East Anglia have developed a new drug that works against the main types of primary bone cancer
  • Cancer that starts in the bones, rather than cancer that has spread to the bone, predominantly affects children and young adults
  • The breakthrough drug increases survival rates in preclinical models by 50 per cent without the need for surgery or chemotherapy

A new drug that works against the main types of primary bone cancer has been developed by researchers at the University of East Anglia and University of Sheffield.

Cancer that starts in the bones, rather than cancer that has spread to bone, predominantly affects children and young adults.      

Current treatment is brutal, with outdated chemotherapy cocktails and limb amputation leading to life-long disabilities.

Even after these gruelling treatments, the five-year survival rate is still poor at just 42 per cent – largely because of how rapidly bone cancer spreads to the lungs. These rates haven’t changed in nearly half a century.

But a new study published in the Journal of Bone Oncology shows how a new drug called ‘CADD522’ blocks a gene associated with driving the cancer’s spread, in mice implanted with human bone cancer.

The breakthrough drug increases survival rates by 50 per cent without the need for surgery or chemotherapy. And unlike chemotherapy, it doesn’t cause toxic side effects like hair loss, tiredness and sickness.

Co-author of the study, Professor Alison Gartland, from the University of Sheffield’s Department of Oncology and Metabolism, said: “Primary bone cancer, although rare, occurs most often in children and young adults between the ages of 10 and 20 usually during a growth spurt. It is a difficult cancer to treat as it can spread very rapidly to other parts of the body - especially the lungs.

“Currently children have to undergo very toxic treatment which has very unpleasant and sometimes life-long side effects and sometimes life-changing amputation. This, coupled with the low survival rate, is why this drug is so incredibly important and could make a huge difference to patients and their families. 

“This breakthrough was only possible due to the extensive collaboration between teams at the Universities of Sheffield and East Anglia and I sincerely hope that with further research and backing this drug can be used in clinical trials in the near future.”

The researchers collected bone and tumour samples from 19 patients at the Royal Orthopaedic Hospital in Birmingham. However, this small number was more than enough to detect some obvious changes in the cancers.

The team used next generation sequencing to identify types of genetic regulators called small RNAs that were different during the course of bone cancer progression. They also showed that a gene called RUNX2 is activated in primary bone cancer and that this gene is associated with driving the cancer’s spread.

They went on to develop CADD522, a small molecule which blocks the RUNX2 protein from having an effect, and tested it in mice.

Lead researcher Dr Darrell Green, from UEA’s Norwich Medical School, was inspired to study childhood bone cancer after his best friend died from the disease as a teenager. 

He said: “In high school, my best friend Ben Morley became ill with primary bone cancer. His illness inspired me to do something about it myself because during my studies I realised that this cancer has been all but left behind others in terms of research and treatment progress. 

“I wanted to understand the underlying biology of cancer spread so that we can intervene at the clinical level and develop new treatments so that patients won’t have to go through the things my friend Ben went through.

“Ultimately, we want to save lives and reduce the amount of disability caused by surgery. And now we have developed a new drug that potentially promises to do just that.”

Dr Green added: “In preclinical trials, metastasis-free survival was increased by 50 per cent using the new CADD522 drug on its own, without chemotherapy or surgery. I’m optimistic that combined with other treatments such as surgery, this survival figure would be increased further.

“Importantly, because the RUNX2 gene is not usually required by normal cells, the drug doesn’t cause side effects like chemotherapy. This breakthrough is really important because bone cancer treatment hasn’t changed for more than 45 years.”

The new drug is now undergoing formal toxicology assessment before the team assemble all of the data and approach the MHRA for approval to start a human clinical trial.

The research was led by UEA in collaboration with the University of Sheffield, Newcastle University, the Royal Orthopaedic Hospital, Birmingham, and the Norfolk and Norwich University Hospital.

The work has been funded by the Sir William Coxen Trust and Big C.

View the full paper


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