The project addresses a clinical problem with a transformative approach to change our current paradigm in preclinical models. Traditional cell culture models utilising cells grown as monolayers have poor biological relevance, particularly for tumour biology. Our biologically relevant approach provides a tissue-like microenvironment to advance preclinical studies. We use a biomaterial-based 3D approach that allows cells to crosstalk with their microenvironment, which initiates critical events at cellular and molecular levels, changes in cell functions, biomechanics and gene expression. In a 3D structure, cells can recreate their original architecture similar to human tissues providing data of clinical relevance for people diagnosed with cancer. Bioengineered 3D models also minimize the use of research animals, and our biomaterials for the 3D cell cultures are ethically sustainable.
This is important for society because more than 90% of anti-cancer drugs brought to the clinic fail. The gap between preclinical evidence and clinical reality arises, partially, from the inability of traditional experimental models to truly and reproducibly recreate the original tissue composition and biomechanical properties of real tumours. Improvements in preclinical research can enable higher success rates and better clinical outcomes for people diagnosed with cancer. To achieve these goals, we need patient-specific and clinically predictive models using patient-derived samples to observe responses to drugs and optimise therapies like precision medicines. For pancreatic cancer, targeting only the tumour cells has failed. Pancreatic cancer is on its way to become the second deadliest cancer. The tumour microenvironment is a crucial untapped therapeutic target but a better understanding of the mechanisms of cell-cell and cell-matrix interactions within the cancer ecosystem is crucial to progress drug discovery and development.
The overall objectives are to combine tumour biology and tissue engineering to design a new platform and to find and test better treatments for pancreatic cancer. We aim to develop a controllable and reproducible technology platform for modelling the human tumour microenvironment of pancreatic cancer in 3D culture. In a complementary strategy, we are using hydrogel-enabled models and patient-derived cells to recreate the matrix composition, architecture and dynamics of pancreatic cancer and metastasis to decipher its tumour biology and improve its treatment.
