As a result of research, cure rates for most cancers have been steadily increasing over the last four decades. However, some remain very difficult to treat and pancreatic cancer is one of these. With the help of a 2018 grant from Cancer Research Trust New Zealand, Professor Christian Hartinger from the University of Auckland School of Chemical Sciences is working hard to meet the need for improved treatment options for pancreatic cancer.

In the early years of cancer chemotherapy, the search was for a “silver bullet” to treat all cancers. While many effective drugs were developed, it is now clear that the best approach is to identify unique molecules expressed by individual cancers and to develop drugs which target these. Cancer cells are just normal cells that have gone “rogue” and the trick is to find targets that are over-expressed on the cancer cells and minimally expressed on normal cells. This approach greatly reduces the collateral damage inflicted on healthy tissue.

One approach is to identify a potential target molecule on a particular cancer and screen existing drugs for their affinity for that molecule. Using this strategy Dr Hartinger and colleagues have established that a group of drugs called plecstatin bind selectively to a molecule called plectin which is highly expressed on the cells of pancreatic cancer.

This graphic is a schematic drawing of the interaction of plecstatin with a plectin domain

Says Dr Hartinger, “Showing that a drug binds to cancer cells is just the first step in the drug-development journey. Plectin is a large protein molecule and plecstatins are small molecules so it is important to know which parts of the target actually bind to the drug. The object is to find the parts of the target which have the highest affinity for the drug, which then allows us to tweak the drug to make it more cancer-cell specific and less toxic to normal cells."

"To do this we needed to synthesis small parts of the plectin molecule and this is the work funded by CRTNZ. We have now made 18 protein constructs and fully characterised these and preliminary studies show that some are highly attractive binding sites for the plecstatin drugs. This project represents the very early stage of drug development, and is the hardest part to get funded."

"But now that we have strong preliminary data we have been able to obtain additional funding to take it to the next stage. We are grateful to Cancer Research Trust New Zealand for the opportunity to look for new ways to treat this very intractable cancer.”

Says Douglas Ormrod, Cancer Research Trust New Zealand Executive Director, “this research is a perfect example of what the Trust is about – we help new ideas to grow so that big advances can be made in the future.”