Cancer Research UK has led an investigation, resulting in the discovery of a mechanism that may explain why pancreatic cancer patients are often resistant to chemotherapy treatment gemcitabine.
It is hoped this study will help scientists overcome a common resistance to gemcitabine and make future chemotherapy drugs more effective.
The scientists at Cancer Research UK's Cambridge Research Institute, co-funded by the Lustgarten Foundation and the National Institute of Health, sought to understand why promising drugs generally fail in pancreatic cancer clinical trials.
They found that a genetically modified mouse model of pancreatic cancer that closely resembles human cancer was also largely resistant to gemcitabine treatment.
The scientists found in these mouse studies that pancreatic cancer is resistant to chemotherapy because the tumours tend to have poor networks of blood vessels called vasculature, which makes it harder for drugs to reach the tumour.
Working with groups at Addenbrooke's Hospital, the Johns Hopkins Hospital, the University of Dresden, M D Anderson Cancer Centre, the University of Pittsburgh and the Fred Hutchison Cancer Research Centre, the group noted that human pancreatic cancer samples also contained a deficient blood supply, suggesting that their observation should also be applicable to patients.
The study also found that the genetically modified mice displayed the same resistance to gemcitabine as seen in human pancreatic cancer, whereas the transplantation mouse models traditionally used to develop chemotherapy treatments were sensitive to gemcitabine.
This means that the genetically modified models could prove superior in developing treatments in the future.
When the scientists used a compound called IPI-926, created by Infinity Pharmaceuticals, in combination with gemcitabine in the genetically modified animals, they noticed increased cell death and a reduction of the pancreatic tumour size.
They believe that using this combination may also reopen the door to several treatments which have, so far, proven disappointing in patient trials for pancreatic cancer because of poor drug delivery.
'But these are early days and we need to show this approach is safe to use in humans before we can consider adding the compound to cancer treatments,' said Dr David Tuveson, group leader in tumour modelling and experimental medicine at Cancer Research UK's Cambridge Research Institute.
These findings may also help to explain why pancreatic cancer does not respond to anti-angiogenic drugs such as VEGF inhibitors, when many other cancers do.
Anti-angiogenics are a class of drugs which starve the tumour by restricting its blood supply.
As pancreatic cancers do not seem to need as good a supply of blood to the tumour as other cancers, the scientists believe that they may need to introduce additional drugs to help stop tumour growth.
