A research team led by Dr Darrell Green, a trustee of the Bone Cancer Research Trust, have identified a new drug that works against all main forms of bone cancer.
Researchers at the University of East Anglia discovered that the drug, called 'CADD522', works by blocking a gene associated with metastatic disease.
Preliminary studies suggest that it can significantly improve survival in advanced laboratory models of bone cancer and gives rise to less toxicity than is seen with standard chemotherapy.
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.
Now, his team have made what could be the most important drug discovery in the field for more than 45 years.
Dr Green said:
Bone cancer can rapidly spread to other parts of the body, and this is the most problematic aspect of this type of cancer. Once it has spread, it becomes very difficult to treat with curative intent. In high school, my best friend Ben Morley became ill with the disease. 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 in terms of research and treatment progress. So, I studied and went through university and obtained my PhD to eventually carry out research in this field. I wanted to understand the underlying biology of cancer spread so that we can intervene at clinical level and develop new treatments so that other 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.
The team collected bone and tumour samples from 19 patients at the Royal Orthopaedic Hospital in Birmingham, a sarcoma specialist centre that is supported by the Bone Cancer Research Trust's Infrastructure Grants. This small number was more than enough to detect some obvious changes in the cancers.
The team 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 also showed that a gene called RUNX2 is activated in bone cancer and this gene is associated with driving the cancer's spread.
They went on to identify a new drug called CADD522, which is a small molecule that blocks the RUNX2 protein from having an effect, and tested it in pre-clinical models.
Dr Green added:
Importantly, because the RUNX2 gene is not usually required by normal cells, the drug doesn't cause side effects like chemotherapy does. This breakthrough is really important because bone cancer treatment hasn't changed in 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 tests have shown that it is not toxic to the rest of the body. This means it would be a much kinder treatment for children with bone cancer, compared to 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 a formal toxicology assessment before the team assemble all of the data and approach the MHRA for approval to start a clinical trial.
Aims of the project
- Determine whether specific parts of a cell's genetic instructions (called small RNAs) can help to explain why primary bone cancer progresses and spreads to other parts of the body.
- Explore whether this can be applied across different types of primary bone cancer (chondrosarcoma, Ewing sarcoma and osteosarcoma), looking at differences in small RNAs as potential hallmarks and drivers of progression.
- Harness these genetic features as potential treatment targets for developing and testing new therapies to stop primary bone cancer progression.
What does this mean for patients?
These are extremely exciting results and represent a significant step towards kinder, more effective treatments for patients with primary bone cancer.
However, experiments have so far been restricted to laboratory models of primary bone cancer and have only focussed on the anti-cancer effect of a laboratory compound.
Before CADD522 can be used to treat patients, a wide range of further in-depth investigations are needed to ensure that it is safe and does not cause toxicity or harmful effects to other bodily organs. Additionally, researchers must establish how to develop the drug in large enough quantities at the required level of purity.
If all goes to plan, this crucial further research and development is likely to take in the region of 3 - 5 years.
This research breakthrough has been published in the Journal of Bone Oncology and can be found at the link below: