Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPSAITO, Renata de FreitasANDRADE, Luciana Nogueira de SousaBUSTOS, Silvina OdeteCHAMMAS, Roger2022-12-212022-12-212022FRONTIERS IN IMMUNOLOGY, v.13, article ID 768606, 24p, 20221664-3224https://observatorio.fm.usp.br/handle/OPI/50486To become resistant, cancer cells need to activate and maintain molecular defense mechanisms that depend on an energy trade-off between resistance and essential functions. Metabolic reprogramming has been shown to fuel cell growth and contribute to cancer drug resistance. Recently, changes in lipid metabolism have emerged as an important driver of resistance to anticancer agents. In this review, we highlight the role of choline metabolism with a focus on the phosphatidylcholine cycle in the regulation of resistance to therapy. We analyze the contribution of phosphatidylcholine and its metabolites to intracellular processes of cancer cells, both as the major cell membrane constituents and source of energy. We further extended our discussion about the role of phosphatidylcholine-derived lipid mediators in cellular communication between cancer and immune cells within the tumor microenvironment, as well as their pivotal role in the immune regulation of therapeutic failure. Changes in phosphatidylcholine metabolism are part of an adaptive program activated in response to stress conditions that contribute to cancer therapy resistance and open therapeutic opportunities for treating drug-resistant cancers.engopenAccesslipid metabolismphosphatidylcholinelipid mediatorsimmunoregulationimmune microenvironmentcancer drug resistancecholine kinase-alphahuman breast-cancermagnetic-resonance-spectroscopyphospholipase-d activitygrowth-factor receptorin-vivodrug-resistanceneoadjuvant chemotherapylysophosphatidic acidhistone deacetylasearticleCopyright FRONTIERS MEDIA SA10.3389/fimmu.2022.768606Immunology