Connecting the cell cycle to lipid metabolism in cancer: Their reciprocal roles and opportunity for therapeutic exploitation

Uncontrolled cellular proliferation is a hallmark of cancer that is both driven by deregulation of the cell cycle, and fueled by metabolic reprogramming. Among the metabolic alterations detected, lipid metabolism is markedly upregulated to provide resources for proliferating cancer cells. Each cell cycle requires lipids for membrane synthesis, energy production, and cellular signaling, yet the mechanistic relationship linking the cell cycle to lipid metabolism in cancer remains incompletely understood. Recent advances in lipidomic technologies that enable comprehensive profiling of the cancer lipidome have provided new insights into the interconnections between these two pathways. This review describes how cell cycle regulators influence various aspects of lipid metabolism in models of cancer and the effect of cell cycle perturbation on cellular lipid profiles. We further describe lipid metabolic changes associated with response and resistance to cell cycle inhibitors in cancer and offer insight into how these findings may inform the development of clinical biomarkers and new therapeutic strategies.