Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Robin Rumney & Prof Dariusz Gorecki, University of Portsmouth
Award: £100,901
Awarded December 2020
Ewing’s sarcoma is the second most common type of bone cancer in young people under 30 years old. Thanks to early treatment with the right combination of surgery, radiotherapy and chemotherapy, up to 70% of patients with localised Ewing’s sarcoma survive five-years from diagnosis.
However, when Ewing’s sarcoma invades other tissues, disease free survival drops below 30%. This demonstrates a clear need for new treatments.
We know that as Ewing’s sarcoma develops, specific changes occur within the tumour that make it more likely to spread. One such change is an increase in the availability of a molecule called DPP-4, which has been linked to tumour growth and spreading. DPP-4 is also found in white blood cells, which sometimes surround the tumour and are associated with more aggressive cancers and worsened patient outcome.
As white blood cells can produce DPP4, it is possible that they are bringing more ‘fuel to the fire’. Coincidentally, DPP-4 also causes problems in diabetes where it disrupts insulin production. Because of this, a family of drugs that inhibit DPP-4 (called gliptins) have recently been developed to treat patients with diabetes.
Because we know DPP-4 in the tumour may worsen outcomes for patients with Ewing sarcoma, we want to investigate the hypothesis: could we reduce the growth of Ewing’s sarcoma by treatment with gliptins?
We will quantify DPP-4 and related molecules from human Ewing’s sarcoma tumours in both tumour cells and surrounding white blood cells. We will also investigate the effects of gliptins on Ewing’s sarcoma cells and white blood cells grown in laboratory conditions.
If our hypothesis is confirmed, this would mean that gliptins could be safely repurposed to block the DPP-4 molecule in Ewing’s sarcoma and thereby potentially reduce the progression of this type of cancer.