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Reprogramming of cellular metabolism is an important, emerging, and universal hallmark ofcancer which has received considerable attention during the recent era of cancer research. Cancer cells show characteristic alterations in glucose metabolism in order to fulfill the needsof biosynthesis for tumor proliferation and growth. However, under certain circumstancessuch as invasion and metastasis, cancer cells are prone to metabolic stress and will requiredifferent strategies to meet the high energetic demand from cancer progression. From variousmetabolic rewiring mechanisms, cancer cells adopt other metabolic pathways with alternativenutrient sources. Therefore, targeting cancer metabolism holds promising but great challengecaused by the metabolic plasticity of cancer cells. This review will discuss characteristic cancermetabolism in detail with special focus on lipid metabolism which is gathering increasinglykeen interest, in order to find novel therapeutic approaches to head and neck cancer. By understandingand exploiting the synthesis, oxidation, and storage of fatty acids, we couldinvestigate potential strategies to block cancer proliferation and progression