Towards effective treatment for pancreatic cancer
Case Study of animal models use to demonstrate the safety of an approach to treat pancreatic cancer.
How we have used animal models to demonstrate the safety of our novel approach to treat pancreatic cancer.
Pancreatic cancer remains one of the most difficult cancers to treat and this is due primarily to the fact that symptoms are rare in the early stages.
When patients do present with symptoms the disease has usually progressed to a relatively advanced stage and as a consequence, is much more difficult to treat. The most common form of pancreatic cancer is adenocarcinoma and in cases where surgery is possible, some 7-25% of people will survive for 5 years or more.
However, because of late presentation only about 8% of people qualify for surgery. For the remainder with locally advanced or metastatic disease and who are not suitable for surgery survival to 5 years or more decreases to about 5%.
In the face of such dismal survival statistics, we are addressing a clear, un-met need for new therapeutic approaches.
Our approach involves the use of lipid shelled microbubbles that will disintegrate in the presence of an externally-applied ultrasound beam.
We fill the bubbles with oxygen and coat the bubble with drugs. Some of those drugs are inactive under normal circumstances. However, when they are stimulated by an ultrasound beam, they become toxic by producing highly toxic compounds known as reactive oxygen species (ROS). This approach is known as sonodynamic therapy (SDT) and we have developed novel approaches that allow us to use this system to deliver SDT, in combination with conventional cancer chemotherapeutic drugs to pancreatic tumours. However, because the conventional cancer chemotherapy drugs are targeted to a specific site using ultrasound, we can use much less and this precludes adverse effects normally associated with such drugs.
Use of animal models
As we progress this work towards clinical trials with pancreatic cancer patients, it has been necessary to demonstrate that the approach is both safe and effective.
We have used animal models to demonstrate the safety of our approach and have shown that no adverse effects have been observed using this approach. We have also demonstrated that the approach can result in the deposition of drugs at a chosen target in animal models.
We have further shown that application of the approach to the treatment of cancer in these animal models results in dramatic reductions in tumour size (Fig.2b). We continue to refine our system using animal models in order to ensure maximum safety and efficacy prior to embarking on trials in patients.