Tissue-engineering the tumour microenvironment to improve treatment of pancreatic cancer

ongoing

My vision is to address a clinical problem with a novel and transformative approach. Using my unique expertise in cell biology, tissue engineering and translational research I will design technology platforms to test new treatments for human pancreatic cancer. Pancreatic tumours are cancers of unmet medical need with 85% of patients dying within 9 months of diagnosis. To find better therapies, we need patient-specific models that mimic the biology of tumour tissues and target interactions between malignant and non-malignant cells. Biomimetic tissue engineering is a powerful approach to generate 3D cancer models, however, only a few scientists use these technologies. Most 3D cultures of human cells include reconstituted matrices that originate from murine tumours containing undefined amounts of extracellular matrix and growth factors. There is no tissue-engineered 3D model that allows control over patient-specific and biomechanical characteristics of the pancreatic tumour microenvironment. I hypothesise that 3D approaches that replicate the native tissue composition and biomechanical properties will behave like real tumours to provide clinically predictive platforms and to test novel treatments that target both malignant and non-malignant cells. To test my hypothesis, I will: •3D-print matrix and cellular elements of the microenvironment of human pancreatic tumours •Develop a cancer-on-a-chip model of liver metastasis •Compare the crosstalk of malignant and other microenvironment components with the human disease •Validate my new platforms with treatments in clinical trials and test novel combination treatments that slow down or reduce tumour growth. In a multidisciplinary project, I will use: •3D printing to build platforms composed of hydrogels, fibrous scaffolds and patient-derived cells •Extracellular matrix molecules for chemical crosslinking into hydrogels •Cancer-on-a-chip models to study tumour metastasis •Imaging, biomechanical and multi-omics analyses.