Dr Sarah McClelland has won PCRF funding to study the mechanisms that drive large-scale changes in chromosomes in pancreatic cancer in fine detail.
This genome shuffling process is thought to provide tumour cells with a way to evade chemotherapy. How pancreatic cancer cells do this is not yet known, and the McClelland lab will build on previous expertise in other cancer types to define pathways involved in pancreatic cancer, and test ways in which this process could be blocked to provide a potential new way to treat genetically unstable cancers.
Prof. John F Marshall
There are no effective therapies for pancreatic cancer and new targets are desperately sought. In previous PCRF-funded research, the Marshall lab confirmed that the integrin alpha-v beta-6 (αvβ6) is on the surface of pancreatic adenocarcinoma tumour cells in 90% of patients.
They had developed a small protein fragment, a peptide called A20FMDV2. They recently showed that this fragment, when bound to a drug, could selectively deliver effective therapy to mice that had αvβ6-positive pancreatic tumours.
Although our preliminary studies suggested no significant toxicity other than to the cancer, before we can consider moving to the clinic we must perform essential experiments to examine whether other organs had been affected at the cellular level. We also aim to establish the relative efficiency of drug delivery and, hopefully, improve it further.
Our animation summarises the importance of integrins in tumour growth and spread:
Dr Tanja Crnogorac-Jurcevic and Dr Nathalie Massat
Dr Crnogorac-Jurcevic’s potential test to diagnose early stage pancreatic cancer, funded by PCRF, made global headlines in 2015 and is nearly ready to start a clinical trial.
The new grant will enable her team to further validate urinary biomarkers (potentially incorporating further molecules called miRNAs) and develop a combined ‘risk score’ for each biomarker in a panel – a crucial step in interpreting clinical trial data and a requirement for the trial to take place.
Industrial CASE Studentship
This award is part of the London Interdisciplinary Doctoral (LIDO) Training Partnersip between several London Universities and commences in October 2017. The new BCI student in Prof. Marshall's group will examine the mechanisms of internalisation of the integrin αvβ6 by bronchial epithelial cells - the cells on the surface of the wind pipe leading into the lungs.
This integrin is responsible for driving fibrosis in the lung and one potential mechanism to reduce fibrosis would be to cause αvβ6to be internalised (taken into the cell). The Marshall lab has found methods to do this.
The project will involve collaboration with Dr Tyson Sharp and Dr Dan Foxler in Molecular Oncology, who will provide training in CRISPR/Cas9 gene knockout technology, and Dr Rob Slack at the Fibrosis Unit GSK, Stevenage.