Modelling the molecular link between high Fat diet, Metabolic reprogramming and Inflammation in Lung Cancer

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Thirty years of cancer genetics have revealed the dominant cancer genes that are mutated in most forms of human cancer. What hasalso become a re-emergent dominant topic of cancer research in the past decade is that most solid tumours undergo reproduciblechanges in their glucose and lipid metabolism that enables rampant growth and foster survival of tumour cells in nutrient limitingconditions. What is less well-understood is how diet and dietary contributions of glucose, fructose and fats intersect with cancergenetics. Western diets and how they can speed cancer development are the topics of this proposal. FaMILC is focused on lungcancer, the most common cause of cancer deaths per year in men and in women in Europe. The metabolic profile of lung cancer isdriven in large part by specific genetic driver events and is highly dependent on de novo fatty acids synthesis. Using cutting edgelipidomic approaches, our goal is to understand to which extent high fat diet connects with tumour cell lipogenesis to favouroxidation of fatty acids and how genetic aberration modulate these links. Lipids, particularly specific classes of sphingolipids, haverecently been shown to be crucial sources of energy for cancer cell growth influencing cancer cell aggressiveness. Furthermore, lipidsare the main source for prostaglandins, mediators of inflammation. High fat diet can perturb immune responses and increaseinflammatory cells through dysregulation of lipid metabolism, oxidative stress and immune pathways. These unnecessaryinflammatory responses can affect downstream cell proliferation, angiogenesis, tumour metastasis and chemotherapeutic response.FaMILC aims to decipher how Western-style diet influences non-small cell lung cancer inflammatory responses and metabolismintersecting with specific genetic alterations to control tumour progression.