Adamantinoma is a rare primary bone cancer that occurs primarily in the shinbone. There are currently no effective treatments for adamantinoma beyond surgery and currently, clinicians are unable to predict which patients are more likely to suffer a recurrence and / or progress to metastatic disease.
Consequently, there is an urgent need for both new treatments options and predictive biomarkers in adamantinoma, which can help monitoring the progression of this type of primary bone cancer.
What are the aims of this research project?
Previous work carried out by Dr Katherine Finegan and her research group research group at the University of Manchester, have already shown that two proteins that act together in cancer cells, named MEK5 and EKR5 (MAPK kinase 5-extracellular signal-regulated kinase 5), are key for the development and spread of osteosarcoma. This project aimed to investigate if MEK5-ERK5 also control adamantinoma development, and if their presence and activity can be a used as new marker, to track the recurrence or spread of adamantinoma. Secondly, the researchers wanted to find out if by targeting MEK5-ERK5 with new drugs being developed, whether this might improve adamantinoma outcomes by preventing MEK5-ERK5 from working in the cancer cells, and therefore stopping cancer cell growth and spread.
FINDINGS
The researchers measured the amount of MEK5-ERK5 in tissue samples taken from patients with adamantinoma, as well as measuring other markers, to allow comparisons to see if MEK5-ERK5 was more switched on and therefore potentially driving the cancer. Not only did they find high levels of ERK5 in these tissue samples, but they also found these high levels were linked to worse outcomes of adamantinoma including recurrence and spread of the cancer. Additionally, in two new cell models of adamantinoma that the researchers developed as part of this research, it was shown that by blocking the MEK5-ERK5 pathway, this could be a promising new treatment strategy for adamantinoma.
CONCLUSIONS AND OUTCOMES FOR PATIENTS
This research is the first ever evaluation of the role of the MEK5-ERK5 signalling pathway and its’ role in adamantinoma. As well as finding abnormally high levels of ERK5 in adamantinoma patient tissue samples, there was a correlation between this and worsening outcomes for patients. By using these finding to test novel drugs to target this signalling activity, these discoveries provide proof-of-concept data for a potential new class of effective treatments for adamantinoma patients.
FUTURE PLANS
The researchers are developing novel ERK5 drugs to treat adamantinoma, with plans to test these in clinical trials in the future, for adamantinoma patients who currently have no treatment options beyond surgery.
Funding for this pioneering research into adamantinoma has been made possible by The Liz Clarke-Saul Fund.
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