New mechanism of drug resistance implies a new animal model need in pancreatic cancer

Research lead

Scientists funded by the charity Cancer Research UK have discovered a new mechanism that may explain why pancreatic cancer patients are often resistant to the chemotherapy treatment gemcitabine.

Using mouse models the scientists found that pancreatic cancer is resistant to chemotherapy because it tends to have poor networks of blood vessels, or vasculature, making it harder for drugs to reach the tumour.  It was also observed that human pancreatic cancer samples have a deficient blood supply.

David Tuveson, group leader in tumour modeling and experimental medicine at Cancer Research UK’s Cambridge Research Institute, said, “These results [...] may help explain the disappointing response that many pancreatic cancer patients receive from chemotherapy drugs.  

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 are sensitive to gemcitabine. This indicates genetically-modified mouse models should be used in developing new treatments.

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. These drug are designed to starve tumours by restricting the blood supply. As pancreatic cancers appear not to need as good a supply of blood as other cancers, restricting blood flow is unlikely to be as effective as in other tumour types.