Researchers at the University of East Anglia and University of Manchester have made an important breakthrough that could lead to ‘kinder’ treatments for osteosarcoma patients.

New research published today has identified a set of key genes that drive osteosarcoma spread to the lungs in patients. In further experiments in mice with engineered human osteosarcoma cells that lack these key genes, the cancer cannot spread to the lungs.

The research was led by Dr Darrell Green, from UEA’s Norwich Medical School and Dr Katie Finegan from the University of Manchester. Both are founding members of OMeNet (Osteosarcoma Metastasis Network) and Dr Green is also a Trustee of the Bone Cancer Research Trust.

Dr Green was inspired to study childhood bone cancer after his best friend died from the disease as a teenager. Now, the team has made what could be the most important discovery in the field for more than 40 years. Dr Green said:

Primary bone cancer is a type of cancer that begins in the bones. It’s the third most common solid childhood cancer, after brain and kidney, with around 52,000 new cases every year worldwide. 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 is very difficult to treat.

Around a quarter of patients have cancer that has already spread by the time they are diagnosed. Around half of patients with apparent localised disease relapse, with cancer spread detected later on. These figures have remained stagnant, with no significant breakthroughs in treatment, for more than four decades.

I want to understand the underlying biology of cancer spread so that we can intervene at the clinical level and develop new treatments so that 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.

There has been extensive research in to identifying the genetic drivers that cause osteosarcoma, however, much less is known about what drives its spread to other parts of the body.

After profiling tumours, circulating tumour cells (CTCs) and metastatic tumours from patient donors, they were able to identify a potential driver for metastasis in osteosarcoma – known as MMP9. MMP9 is known to be a controller of metastasis in a number of solid cancers, however, it's influence on the metastatic process in osteosarcoma has not been fully understood. Dr Green said:

This driver that we identified is well known in cancer, but it is also considered ‘un-druggable’ because the cancer quickly becomes resistant to treatment, or it finds a way to escape being targeted. So we thought we would try something different and find the ‘master regulator’ of MMP9 so that we could ‘action’ the ‘un-actionable’.

The team began collaborating with researchers at the University of Manchester who were working on the proposed master regulator of MMP9 - MAPK7 - in several cancers using mouse models, including osteosarcoma.

Together, they engineered human osteosarcoma cells to contain a silenced version of MAPK7. They found that when these cells were put into mice, the primary tumour grew much more slowly. Importantly, it didn’t spread to the lungs – even when the tumours were left to grow for a long time.

Senior author Dr Katherine Finegan from the University of Manchester said:

It has been great to work together with Dr Green and the team at UEA. Using their genetic insights from patient material, we were able to validate their work in models of primary bone cancer. As a result, we have highlighted a potential new way to treat metastatic bone cancer by targeting a key protein that promotes metastases. This work has uncovered a novel treatment option for osteosarcoma, something we have not had for the last 40 years.

In the Finegan lab we are already in the process of developing new drugs against MAPK7, which we hope to implement for the benefit of primary bone cancer patients in the future. We would also like to thank the charity Friends of Rosie who funded the work in the Manchester lab and support childhood cancer research here in the North West.

Dr Zoe Davison, Head of Research, Information & Support, Bone Cancer Research Trust, said:

This work marks an incredibly significant find in the fight against osteosarcoma. We are delighted that we were able to introduce and bring the research team together so that they could complete this vital work. More and more we are seeing how greater collaboration and co-working is unlocking potential ways to fight primary bone cancer, save lives and improve outcomes for all our patients.

Super Strong Sophie

One of the patients who donated tissue to the study was five-year-old ‘Super Strong’ Sophie Taylor from Norwich. She was first diagnosed with osteosarcoma in January 2018, and underwent surgery to amputate part of her leg, as well as chemotherapy. Sadly Sophie was taken to hospital with breathing difficulties a year after diagnosis at the beginning of January 2019, where her family were told there was extensive cancer in her lungs. She passed away on January 18, 2019.

Sophie’s dad, Alex Taylor said:

Sophie was diagnosed with Osteosarcoma in January 2018. Unfortunately it was in her lungs at the time it was found. When we were informed necrosis from chemotherapy was low, we embarked on finding additional options and were fortunate to come into contact with Dr Green.

We did not hesitate in offering Sophie's tumour for research and to also have her DNA and RNA analysed to link it to additional drugs to pursue. It gave us hope and it was amazing to have Dr Green fighting in our corner.

Sophie's full story will be shared by the Bone Cancer Research Trust later this month as part of #SarcomaAwareness Month on what would have been her 7th birthday.