In this exclusive interview with Dr Katie Finegan from the University of Manchester, we find out more about how the research team will aim to validate a key pathway, which could cause the spread of adamantinoma, alongside testing drugs, which the team have already identified to be effective at stopping the spread in osteosarcoma, to see if they could work for adamantinoma patients.

Can you tell us a bit about yourself?

I have a pharmacy background, which provides you with the knowledge of how to develop medicines, how to use medicines and how to be safe with medicines. After finishing my degree, I returned to University and completed a masters, followed by a PhD investigating cell signalling pathways that led me into the field of cancer and running my own research group. The work carried out in our lab investigates the signals that cancer and immune cells release and how we can interfere with those signals to treat cancer.

Can you tell me about the project and its aims?

Primary bone cancer is rare and adamantinoma is one of the rarest types. We have reviewed what is known about it from a biological point of view for example, what makes the cancer be like it is and why does it spread and not respond to treatment, which unfortunately is sometimes the case.

We then looked at the processes that are happening inside the cells and we found that many of them are controlled by a pathway we have already researched in my group called MEK5-ERK5. We know this pathway is important in other cancers; clinical studies have shown that excessive activation of this pathway results in a lack of response to treatment and tumours progress and spread. We have demonstrated that in other cancers, including osteosarcoma, this signalling pathway is key for the development and spread of tumours.

Our aim is to validate if the MEK5-ERK5 pathway also drives the progression of adamantinoma. Once we confirm this, we will test if drugs that inactive the pathway, which we are currently studying and are effective in osteosarcoma, can also work in adamantinoma.

Initially we will be using 20 patient samples, which have been made available by the Infrastructure Grants, funded by the Bone Cancer Research Trust. From these samples we will extract the cancer cells, grow them in the laboratory and then test if the drugs successfully kill the cancer cells.

In other bone cancers like osteosarcoma, the amount of MEK5-ERK5 proteins inside the tumour cells correlates to how well the patient is going to respond to treatment, or if they are going to require more aggressive treatment. Therefore, a second aim of the project is to evaluate MEK5-ERK5 as a prognostic biomarker. We want to study if this is also the case in adamantinoma, and to use it as a new marker to potentially predict which patients are not going to do so well and tailor their treatment accordingly.

The 20 samples from patients we will use for this project are from patients with early disease, localised disease and from patients for whom the disease has spread; we will try to correlate the presence and activation of MEK5-ERK5 with those outcomes, to find a new biomarker that can help clinicians decide how best to treat adamantinoma patients.

We also want to study the immunological effects associated with these signalling pathways. Within the patient samples, in addition to bone cancer cells, there are also immune cells that accumulate around the tumour. We will investigate if there is any interplay between the immune cells and the cancer cells in which the MEK5-ERK5 pathway is involved and can be explored as a potential new target for treatment.

Extracting cells from a patient’s primary tumour is a very challenging process in the laboratory. We are working with Professor Alison Gartland, from the University of Sheffield, who already, has expertise in doing this for other primary bone tumours and will help us with the technique. We are also collaborating with Dr Darrell Green from the University of East Anglia to extract and analyse RNA from the adamantinoma samples, to see if we can spot differences between the samples of patients that present with different stages of the disease.

What do you think this could mean to future adamantinoma patients?

The research aims to validate MEK5-ERK5 pathway as a new therapeutic target; there is a drug already in phase two clinical trial targets that inactivates this pathway. We are also making new inhibitors of the MEK5-ERK5 proteins that are at the in vivo stage of research, although not ready for clinical trial yet.

Our novel inhibitors completely block all the cellular signals mediated by the MEK5-ERK5; so far, we have found that when treated with our inhibitors, osteosarcoma cells die within a week, a more profound effect that we see with any other drugs that target this pathway. This research project will provide the evidence base needed to determine if they could also potentially be used for adamantinoma.

We have already demonstrated in laboratory in vivo models that targeting this pathway in osteosarcoma reduces the spread to the lungs. So, the ideal result would be to extend this effect to block the spread of adamantinoma.

Message to the supporters of the Liz Clarke-Saul Fund

It would not happen without them, if it had not been for Liz and her family and friends fundraising, then we simply would not be able to do it at all. We have the opportunity with our novel drugs, but unless we get the funds needed to test them on different cancers like adamantinoma, we won’t know if we could use them for these patients. This funding has opened that door of opportunity to try and get something we know works well for cancer in principle and see if we can use it specifically to treat adamantinoma.

Funding for this pioneering research into adamantinoma has been made possible by The Liz Clarke-Saul Fund.