The Norwegian Cancer Society’s National Group of Expertise on Pancreatic Cancer (Kreftforeningens nasjonale ekspertgruppe på pancreaskreftforskning – KNEP)
This national consortium encompasses nine research groups that work with pancreatic cancer and now bundle their activities in the context of this 5-years´project. The research portfolio of KNEP comprises studies in the clinical fields of surgery, oncology and medical genetics, in addition to laboratory-based studies on multi-omics characterization of tumour tissue, high-throughput drug screening, histopathology, metabolomics, and animal models for pancreatic cancer. The work package on pathology focuses on morphological and molecular tumour heterogeneity.
PANCAIM – Pancreatic cancer Artificial Intelligence for genomics and personalized Medicine
The aim of this EU-funded project is to use artificial intelligence (AI) to assist clinical decision-making through improved prediction of treatment response and patient outcome. AI will be used for the integration of multi-omics, radiomics and pathomics, the three pillars of personalized medicine. Data will be extracted from a joint pan-European repository with close to 6000 pancreatic cancer patients. Project start: March 2021.
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, proteomics and metabolomics. In the patient cohort of the NorPACT-3 study, tissue metabolomics are correlated with serum metabolomics. Quantitative assessment of the residual cancer burden is assessed in collaboration with the ISGPP (see list of collaborations).
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, 2D- and 3D-(co-)cultures of primary and commercially available 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.
Tumour heterogeneity in pancreatic cancer: transcriptional subclassification and tumour metabolism.
Molecular and metabolic inter- and intratumour heterogeneity is likely an important cause of treatment failure in pancreatic cancer. In this study, a panel of antibodies interrogating the glycolytic and oxidative phosphorylation pathways are employed on paraffin embedded tissue sections in order to map metabolic activity of the cancer and study the association between tumour histomorphology, transcriptional subtypes and metabolic properties. This basic knowledge may contribute to improved pathology assessment and subclassification of pancreatic cancer and possibly to a more individualized and effective treatment for these patients. In the context of the NorPACT-3 study (PI: KJ Labori, Section of HPB surgery, Oslo University Hospital), expression levels of Glut1 (which is part of the glycolytic pathway) in the residual cancer following neoadjuvant chemotherapy will be correlated with the results of FDG-PET/CT scanning.
Spatial digital profiling for the assessment of intratumour heterogeneity in pancreatic cancer
One of the hallmarks of pancreatic cancer is the pronounced intratumour heterogeneity, both in the cancer cell population and the tumour microenvironment. Spatial digital profiling offers a unique possibility to spatially analyse proteins and RNA transcripts. In a first pilot project, RNA transcripts from cancer cells, cancer-associated fibroblasts and leukocytes are analysed and compared between the centre and periphery of the tumour. This project is undertaken in collaboration with Prof. Elin Kure (Institute for Cancer Research, Oslo University Hospital).
Characterization of the genomic landscape and morphological phenotype of pancreatic cancer in patients with hereditary predisposition
In the context of the PREPAIRD study (Personalized surveillance for Early detection and prevention of Pancreatic cAncer in high Risk inDividuals; PI: EM Grindedal, Medical Genetics, Oslo University Hospital), pancreatic cancer from germline-mutation carriers will be characterized in-depth by genomic and transcriptional profiling as well as detailed morphological subtyping.
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.