Breakthrough bone cancer drug could increase survival rate

A research team led by the University of East Anglia (UEA) has developed a new drug that works against all of the main types of primary bone cancer, with their results published in the Journal of Bone Oncology.

Cancer that starts in the bones, rather than cancer that has spread to bone, predominantly affects children and young adults. Treatment is gruelling, with outdated chemotherapy cocktails and limb amputation leading to lifelong disabilities, and the five-year survival rate is just 42% — largely because of how rapidly bone cancer spreads to the lungs.

“Primary bone cancer is … the third most common solid childhood cancer, after brain and kidney, with around 52,000 new cases every year worldwide,” said lead researcher Dr Darrell Green, from UEA’s Norwich Medical School, who was inspired to study childhood bone cancer after his best friend died from the disease as a teenager.

“It can rapidly spread to other parts of the body, and this is the most problematic aspect of this type of cancer. Once the cancer has spread, it becomes very difficult to treat with curative intent.”

Green and his team collected bone and tumour samples from 19 patients at the Royal Orthopaedic Hospital in Birmingham. They then used next-generation sequencing to identify types of genetic regulators called small RNAs that were different during the course of bone cancer progression.

They showed that a gene called RUNX2 is activated in primary bone cancer and that this gene is associated with driving the cancer’s spread. From this, they developed the drug CADD522 — a small molecule which blocks the RUNX2 protein from having an effect — and tested it in mice.

“In preclinical trials, metastasis-free survival was increased by 50% using the new CADD522 drug on its own, without chemotherapy or surgery,” Green said. “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.

“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.”

The drug is now undergoing formal toxicology assessment before the team assemble all of the data and approach the Medicines & Healthcare products Regulatory Agency (MHRA) for approval to start a human clinical trial.

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