Tumour heterogeneity in pancreatic cancer
There is growing evidence that marked inter- and intratumour heterogeneity in pancreatic cancer is a prominent cause for treatment failure. While various taxonomy classifications based on transcriptomics have been proposed, morphological heterogeneity has not been given attention, despite the fact that it is both exceedingly common and pronounced. In this project, four distinct morphological patterns of pancreatic cancer are characterised by a panel of structural and functional features of both the tumour cell population and tumour stroma. Preliminary results show that differences in morphology reflect significant divergence in processes that are deemed to play a central role in the aggressive biology of pancreatic cancer.
Effect of neoadjuvant treatment on pancreatic cancer
In more than 80% of patients, disease is advanced at the time of diagnosis, such that surgery is no longer possible and chemotherapy remains the only treatment option. Unfortunately, the vast majority of patients have very limited benefit from cytotoxic treatment. With the advent of neoadjuvant treatment, the residual tumour tissue, i.e., the part of the cancer that is or has become resistant to treatment, can be characterised and investigated in surgical resection specimens. In this project, intratumour heterogeneity in the residual cancer is investigated by detailed topographic mapping, quantitative assessment of the residual cancer burden, and characterisation of proliferative activity.
Ex vivo culture model of precision-cut pancreatic cancer tissue slices
Given the important role of tumour-stroma interactions in the response to treatment, experimental models should ideally include the tumour microenvironment. In this project, 250 micron thick slices of fresh human pancreatic cancer tissue are cut on a vibrating microtome and kept in culture for up to 48 hrs. This allows for studying the effect of various therapies on the cancer cell population, the tumour microenvironment, and the interactions between both.
Metabolic rewiring and chemoresistance in pancreatic cancer
Recent evidence indicates that pancreatic cancer cells alter their metabolic pathways and use unorthodox strategies for nutrient acquisition in order to survive the deeply hypoxic and nutrient-poor tumour microenvironment. In this project, (co-)cultures of primary human pancreatic cancer cells and stromal cells will be used to investigate the altered metabolic pathways, the role of the stromal cells in the metabolic reprogramming, and the possible link with chemoresistance.
Implementation of new technologies and software systems for whole slide analyses of gastrointestinal cancers
With the growing awareness that spatial relationship is a key determinant in any biological process, the need for multiplex in situ investigation and automated quantitative assessment has led to the development of new technologies that are currently being implemented in several of our research studies. The Hyperion Imaging System (imaging mass cytometry) is used for the study of gastrointestinal cancers with the goal of finding novel prognostic biomarkers. QuPath software for whole slide image analysis is employed to study the expression of DNA repair proteins in colorectal cancer.