Ewing sarcoma is the second most commonly diagnosed form of bone cancer in children, teenagers and young adults. Treatment often includes radiotherapy and recent advances have shown promise for new drugs known as Temozolmide (TMZ), Topotecan and Irinotecan.
Professor Curtin has an interest in improving the effectiveness of established cancer drugs by combining these with ‘PARP inhibitors’. This work explored the possibility of combining known Ewing Sarcoma drugs combined with PARP inhibitors to produce enhanced anti-tumour effects.
What are PARP inhibitors?
PARP inhibitors prevent the repair of DNA breaks that are caused by chemotherapy agents and radiotherapy. This increases the effectiveness of radiotherapy and chemotherapy treatments options such as Temozolomide, Topotecan and Irinotecan. This project, carried out at Newcastle University, aimed to determine if a developed PARP inhibitor (called AG014699) sensitises Ewing sarcoma tumours to radiotherapy and these chemotherapy drugs as previous studies into other cancers have suggested.
This investigation focused on studying Ewing sarcoma cells inside of the laboratory, in the the hope that results would provide support for clinical studies to take place using PARP inhibitors as a combination therapy with radiotherapy, Temozolomide, Topotecan or Irinotecan to enhance the effects of these treatments.
The results of this study were promising and the research group hope to attain further funding to research this area on a larger scale. With PARP inhibitors available through pharmaceutical companies, the correct evidence that this could benefit Ewing sarcoma patients could led to a quicker route to clinical trials in patients.
This work ran alongside the work of Dr Britta Vormoor, who investigates PARP inhibitors; another molecule with a large role in DNA repair. These two projects produced a publication in 2014 reviewing the benefit of inhibiting DNA repair molecules in treating Ewing sarcoma in combination with other treatments, you can read this here.