Lipid metabolism alterations and ferroptosis in cancer: Paving the way for solving cancer resistance

Cancer often perturbs lipid metabolism, which leads to the alteration of metabolism intermediates, contributing to their deregulated growth and metastasis. Alteration of lipid metabolism shifting to contain more polyunsaturated fatty acids (PUFAs) in membrane phospholipids (PLs) also leads to cancer therapy resistance. High amounts of PL-PUFAs render cancer cells more vulnerable to lipid peroxidation (LPO), predisposing them towards ferroptosis, a new form of iron-dependent oxidative regulated cell death. The commitment of cancer undergoing ferroptotic cell death depends on the adaptive lipidome remodeling, LPO patterns, and LPO scavenging ability in heterogeneous cancer cells. Ferroptosis is receiving attention in cancer research as treating cancers, altering membrane lipid homeostasis, and refractory from conventional therapies. Therefore, a better understanding of the molecular underpinning of lipid metabolism alterations may provide new opportunities for solving cancer resistance. This review intends to understand altered lipid metabolism in cancers and discuss lipid composition and metabolic processes associated with ferroptosis induction in cancers.