Kamphorst Jurre J

Cancer is fundamentally a disease of uncontrolled cell proliferation. As a result, cancer cells have an incessant drive to produce building blocks (DNA, proteins and lipids) for the construction of daughter cells. The 'preferred' nutrients for the synthesis of these building blocks are glucose and amino acids, but the demand by rapidly growing tumours often outstrips the supply, causing metabolic stress. This is particularly true for pancreatic cancer, which is characterised by poor blood perfusion and high interstitial pressure. We are interested in understanding how the stressful conditions imposed by the tumour microenvironment affect the metabolism of cancer cells. Our hypothesis is that such metabolic stress responses are tumour specific and can therefore be exploited for cancer therapy. Our approach is to apply a variety of analytical technologies (metabolomics, lipidomics and proteomics) to sophisticated cancer models that are relevant to our research question. The collection of analytical approaches that we use, enable us to progress from initial discovery of the involvement of novel molecules/pathways to an in depth and quantitative interrogation of the observed changes and their functional significance. Using the methodology described above, we found that cancer cells can cope with low nutrient conditions by scavenging extracellular macromolecules (i.e. proteins and lipids) to survive and grow. An important theme in our lab now is the elucidation of the metabolic scavenging pathways and the enzymes involved, determining the conditions in which these pathways are important, as well as establishing the effect of interfering with these pathways on tumour growth.