A collaboration between researchers at the Universities of Manchester and East Anglia have made an important discovery that could lead to kinder treatments for osteosarcoma patients. The researchers were supported in making this discovery by the Royal Orthopaedic Hospital and Infrastructure Grant funding from the Bone Cancer Research Trust.

This important research was led by Dr Katie Finegan (University of Manchester) and Dr Darrell Green (University of East Anglia), both founding members of OMeNet (Osteosarcoma Metastasis Network), a group of current and past Bone Cancer Research Trust funded academics working together, to share knowledge, develop ideas and obtain further funding to advance pre-clinical research into osteosarcoma and other primary bone cancer metastasis. Dr Green is also a Trustee of the Bone Cancer Research Trust.

The team compared primary with metastatic tumours and circulating tumour cells from osteosarcoma patients, and identified high levels of the MMP9 protein, a known controller of metastasis in several solid cancers.

This observation directly points towards using drugs that inactivate MMP9 as a treatment option to reduce the spread of osteosarcoma. Unfortunately, MMP9 inhibitor drugs have had limited success in clinical trials for other cancers. Facing this dilemma, the researchers adopted another approach.

The MAPK7 gene is responsible for the production of MMP9 and other proteins. Using gene editing techniques, they silenced the MAPK7 gene in osteosarcoma cells, and saw a strong reduction in their potential to grow and spread. When these altered cells were explored further, tumours grew much more slowly and did not spread to the lungs. Dr Finegan is now developing drugs against the MAPK7 protein that will hopefully benefit primary bone cancer patients in the future.

Dr Finegan, said:

We are indebted to the Bone Cancer Research Trust for their new initiative: OMeNet. This new co-operative has already yielded great results with mine and Dr Green’s team, working together to make the first big breakthrough in osteosarcoma in nearly 40 years, by together identifying new treatment possibilities for osteosarcoma. This work would not have been possible without the research vision and support of the Bone Cancer Research Trust.

Dr Green, said:

Teams of experts and institutions operating within individual niche expertise must work together to put together the pieces of nature’s broken puzzle. Only then we will see the ‘big picture’ in order to correct the broken pieces, develop novel treatments and significantly improve survival rates.

The Royal Orthopaedic Hospital supported this research through the identification and consenting of 50 patients between 2017 and 2020, meticulously collecting tissue samples and associated clinical data for the project, which was only made possible thanks to Bone Cancer Research Trust Infrastructure Grants. Carolyn Langford, Head of Research, Audit and Development a the Royal Orthopaedic Hospital, said:

The Infrastructure Grants ensures that the essential research staff and processes are in place within the Royal Orthopaedic Hospital to provide high quality research specimens to projects such as Dr Finegan’s and Dr Green’s.

Find out more about how funding provided by the Bone Cancer Research Trust enables research and supports the team at the Royal Orthopaedic Hospital.

This research breakthrough has been published in the Oncogene Journal and can be found at the link below.

Research Paper