Researchers at the University of East Anglia (UEA) in Norwich, U.K. have developed a new drug effective against all main types of primary bone cancer based on blocking a gene upregulated in primary osteosarcomas.
Primary bone cancer is a type of cancer that starts in the bones, rather than spreading there and predominantly affects children. Current therapeutic approaches usually involve chemotherapy and amputations with a five-year survival rate of just 42 percent, revealing the need for less invasive treatments.
Reporting in The Journal of Bone Oncology, a team of scientists at UEA has now been able to show that a new drug called CADD522 significantly reduces tumour volume, increases overall and metastasis-free survival and reduces cancer-induced bone disease in xenograft mouse models.
The drug works by inhibiting a gene called RUNX2 responsible for osteoblast differentiation in the process of bone formation. Before using CADD522 to target the gene, the scientists collected bone and tumor samples from patients at the Royal Orthopedic Hospital in Birmingham and identified RUNX2 as an activator of primary osteosarcoma due to upregulation.
“In preclinical trials, metastasis-free survival was increased by 50 percent 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,“ said Darrell Green, PhD, molecular biologist at Norwich Medical School and first author of the study in a press statement.
According to the scientists, a benefit of CADD52 compared to chemotherapy is its lack of side effects due to the RUNX2 gene not usually being required by healthy bone cells. Using next generation sequencing, the researchers additionally identified small RNAs that also contribute to bone cancer progression and that can be targeted using CADD52.
“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.”
“This breakthrough is really important because bone cancer treatment hasn’t changed for more than 45 years,” Green added.
The researchers say that the drug is currently undergoing toxicological assessments before the team can approach the Medicines and Healthcare products Regulatory Agency (MHRA) for approval to start a human clinical trial.