Combined sonodynamic and antimetabolite therapy for the improved treatment of pancreatic cancer using oxygen loaded microbubbles (U537)

Monday, 23 January 2017

Scientists at Ulster University and University of Oxford have made a major breakthrough in the global fight against pancreatic cancer, the fourth most common cause of cancer-related deaths globally. The work, led by researchers at Ulster University, has revealed the potential of a new, minimally invasive treatment, activated by harmless sound waves, also known as ultrasound.

Problem Being Solved

Survival statistics for pancreatic cancer have not changed in over 40 years with less than 20% of patients surviving 5 years or more.

Diagnosis of the disease tends to be at a late stage and as a result only 20% of patients have surgically resectable disease. A further 31% of patients have locally advanced (LAPC) or borderline resectable (BRPC) disease and 49% have metastatic disease. For those patients with LAPC or BRPC, neoadjuvant therapy (i.e. chemotherapy before surgery) can be used to downstage (i.e. shrink) the tumour and increase the likelihood of resection. This normally involves the systemic administration of toxic chemotherapy drugs that often possess no form of tumour targeting, resulting in off-target toxic side effects.

Technology

Data from our laboratory have shown that targeted SDT/ antimetabolite therapy using our microbubble platform as a delivery system results in a significant reduction in the size of pancreatic tumours with no evidence of acute toxic effects when compared to either SDT or antimetabolite therapy alone.

This reduces MB distribution elsewhere in the body minimising side effects. Both SDT and antimetabolite therapy attack cancer cells using different mechanisms leading to an improved therapeutic effect.

Combined SDT/antimetabolite therapy has been shown in laboratory studies to produce substantially better tumour reductions than the benchmark pancreatic cancer chemotherapy gemcitabine.

Benefits/Applications

Our technology has three key differentiating features:

              The use of SDT as an anti-cancer treatment. The closest competing technology to SDT is photodynamic therapy (PDT) which is approved for the treatment of non-melanoma skin cancer. However, PDT is severely limited by the inability of light to penetrate deeply through human tissue meaning is not indicated for the treatment of deeply seated or larger solid tumours. SDT overcomes this disadvantage as low-intensity ultrasound can penetrate tens of centimetres through soft tissue.

              The use of O2 MBs as a delivery vehicle for attached payloads and encapsulated O2 gas to enable focused delivery of drugs and improve oxygenation in hypoxic pancreatic cancer tumours. This is particularly relevant since SDT requires oxygen as a substrate for the generation of cytotoxic reactive oxygen species. While other groups are investigating the use of MBs as drug delivery vehicles, there are no examples of where a MB has been used to deliver a sensitiser and chemotherapy simultaneously for pancreatic cancer or any other cancer.

              The combination of SDT with a second anti-cancer treatment (antimetabolite therapy) for improved treatment response by killing pancreatic cancer cells using two different cell-death mechanisms.

Publications

Conor McEwan, Sukanta Kamila, Joshua Owen, Heather Nesbitt, Bridgeen Callan, Mark Borden, Nikolitsa Nomikou, Rifat A. Hamoudi, Mark A. Taylor, Eleanor Stride,  Anthony P. McHale, John F. Callan (2015) Combined sonodynamic and antimetabolite therapy for the improved treatment of pancreatic cancer using oxygen loaded micro bubbles as a delivery vehicle. Biomaterials. Vol 80, Pages 20–32.

Press release: http://www.bbc.co.uk/news/uk-northern-ireland-34839453

 

Opportunity/Partnership Sought

Ulster University is actively seeking a strategic partner to assist in the further development of this exciting technology, providing a route to market for the safe and effective treatment of deep tissue tumours such as pancreatic cancer.

 The University is open to a variety of models for collaboration including sponsored research, out-licensing and co-development. In addition, the inventors of this technology are able to provide valuable know-how in order to assist with its successful commercialisation.

For more information please contact:

Dr Oonagh Lynch

Technology Commercialisation Executive

Research & Impact

Tel: +44 (0) 28 9036 6707

Mob: +44 (0) 77 6536 3191

Email:ot.lynch@ulster.ac.uk