Reprogrammed lipid metabolism in advanced resistant cancers: an upcoming therapeutic opportunity

Resistance of cancer to therapy is the main challenge to its therapeutic management and is still an unsolved problem. Rearranged lipid metabolism is a strategy adopted by cancer cells to counteract adversity during their evolution toward aggressiveness and immune evasion. This relies on several mechanisms, ranging from altered metabolic pathways within cancer cells to evolved dynamic crosstalk between cancer cells and the tumor microenvironment (TME), with some cell populations at the forefront of metabolic reprogramming, thereby contributing to the resistance of the whole ecosystem during therapy. Unraveling these mechanisms may contribute to the development of more effective combinatorial therapy in resistant patients. This review highlights the alterations in lipid metabolism that contribute to cancer progression, with a focus on the potential clinical relevance of such findings for the management of therapy resistance.