Pancreatic Cancer Therapeutics Research Program

Utilising clustered regularly interspaced short palindromic repeats (CRISPR) gene editing of tumours, our program will identify critical new cancer vulnerabilities, and promising new targets. CRISPR gene-editing tools play an important role in the discovery of novel drug targets and cancer dependencies, with direct implications for the design of optimal treatment strategies in precision medicine. By integrating CRISPR editing with single cell sequencing techniques, we will be able to systemically assess how complex mutational landscapes and tumour heterogeneity influence and impair functional immune response, and identify new ways of turning on anti-tumour immunity.  

Our researchers are labelling tumours using advanced barcoding techniques to investigate the mechanisms that drive pancreatic cancer metastasis. In this project, our vision is to identify the molecular features of malignant clones within a growing tumour that ‘seed’ lethal metastasis – and the permissive features of the surrounding cancer environment that allow this seeding – to identify new therapeutic vulnerabilities. This will lead to (1) testing of new treatments that target and suppress pancreatic cancer metastasis and (2) identification of potential new contemporary biomarkers for inclusion in future clinical trials. 

Our program is developing and applying state-of-the-art preclinical pipelines for testing and validation of novel, personalised therapeutics. These include bioprinted 3D co-culture systems as living replicas of tumours, for effective high-throughput screening of novel treatments. These models are coupled with living biobanks of patient-derived models of cancer in clinical areas of unmet need, including: pancreatic (>80 patient-derived models already established) and head and neck (>30). These patient avatars are enabling generation of vital proof-of-concept treatment efficacy data required for the clinical translation of our discoveries as part of our bench-to-bedside strategy. Finally, establishment of fully immune-humanised models – that is, a mouse with a human patient-derived tumour and human immune cells, will strengthen our drug development capacity for translation into immune-oncology clinical trials for a range of difficult-to-treat cancers. 

We plan to couple clinical trials with deep correlative science to: (i) identify accurate companion biomarkers that will guide tailored administration of novel therapies; (ii) provide new biologic insights to understand the basis of drug response and equally importantly, clinical treatment failure and (iii) develop new opportunities to combine targeted therapies and plan next-generation studies.   

A complementary, well-annotated repository and analytic pipeline of biological samples from oncology patients recruited as part of our planned novel therapeutic trials will support the research into gaining a comprehensive understanding of the dynamics of treatment response as well as evolution of treatment resistance, to identify new, effective ways of circumventing or targeting this resistance.