Cancer that starts in the bones, rather than cancer that has spread to the bones, predominantly affects children and current treatment is gruelling, with outdated chemotherapy cocktails and limb amputation.

Despite all of this, the five-year survival rate is poor at just 42 per cent – largely because of how rapidly bone cancer spreads to the lungs.

But now a new study 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 research, published today in the Journal of Bone Oncology, was led by UEA in collaboration with Newcastle University, University of Sheffield, Royal Orthopaedic Hospital, Birmingham, and the Norfolk and Norwich University Hospital.

Survival rates increase

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.

The team has made what they say could be the most important drug discovery in the field for more than 45 years.

David Elliott, Professor of Genetics at Newcastle University, said: “Our research has made a significant breakthrough in the treatment of bone cancer, and this is a very exciting development.

“The research shows that basic research into molecular mechanisms of disease can lead to new ways to treat patients.

“It is a really important advance since current treatments for these particular bone cancers have not changed for many years.”

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 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 a new drug, called CADD522, a small molecule which blocks the RUNX2 protein from having an effect and tested it in mice.

Important breakthrough

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 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 that we have developed is effective in all of the main bone cancer subtypes, and so far, our experiments show that it is not toxic to the rest of the body. This means that it would be a much kinder treatment for children with bone cancer, compared to the gruelling chemotherapy and life changing limb amputation that patients receive today.

“We hope it will save a lot of lives.”

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

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

Reference

YBX1-interacting small RNAs and RUNX2 can be blocked in primary bone cancer using CADD522. William Fraser et al. Journal of Bone Oncology.