Research projects
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, tumour metabolism and AI-based morphological analysis
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. As part of the PANCAIM project (see above) and in collaboration with Prof. Ke Yuan and his team at the University of Glasgow, morphological heterogeneity is analyzed with a self-supervised deep-learning approach.
Lymph node metastasis in pancreatic cancer: spatial and single-cell analysis
Lymph node metastasis (LNM) occurs in 70% of patients with resectable pancreatic cancer and represents the strongest prognostic factor in this group. Yet, research has focused exclusively on the primary tumour, leaving important questions unanswered: Are LNMs identical to the primary tumor, or do they differ in morphology, transcriptional subtype, metabolic activity, the stromal compartment or immune microenvironment? What is the impact of neoadjuvant therapy on LNM? Does LNM contribute to subversion of systemic anti-tumor immunity? Does current routine pathology examination adequately reflect the lymph node metastatic burden? While research on LNM in PC has been hampered by the difficulty of obtaining fresh tissue samples and the lack of animal modes, new high-resolution profiling techniques are now applied to a vast archival bank of FFPE tissue.
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.