Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPSIMABUCO, F. M.MORALE, M. G.PAVAN, I. C. B.MORELLI, A. P.SILVA, F. R.TAMURA, R. E.2019-03-132019-03-132018ONCOTARGET, v.9, n.34, p.23780-23823, 20181949-2553https://observatorio.fm.usp.br/handle/OPI/31056The tumor cell changes itself and its microenvironment to adapt to different situations, including action of drugs and other agents targeting tumor control. Therefore, metabolism plays an important role in the activation of survival mechanisms to keep the cell proliferative potential. The Warburg effect directs the cellular metabolism towards an aerobic glycolytic pathway, despite the fact that it generates less adenosine triphosphate than oxidative phosphorylation; because it creates the building blocks necessary for cell proliferation. The transcription factor p53 is the master tumor suppressor; it binds to more than 4,000 sites in the genome and regulates the expression of more than 500 genes. Among these genes are important regulators of metabolism, affecting glucose, lipids and amino acids metabolism, oxidative phosphorylation, reactive oxygen species (ROS) generation and growth factors signaling. Wild-type and mutant p53 may have opposing effects in the expression of these metabolic genes. Therefore, depending on the p53 status of the cell, drugs that target metabolism may have different outcomes and metabolism may modulate drug resistance. Conversely, induction of p53 expression may regulate differently the tumor cell metabolism, inducing senescence, autophagy and apoptosis, which are dependent on the regulation of the PI3K/AKT/mTOR pathway and/or ROS induction. The interplay between p53 and metabolism is essential in the decision of cell fate and for cancer therapeutics. © Simabuco et al.engopenAccessChemotherapyDrug resistanceMetabolismMutant p53P53antineoplastic agentceruleningrowth factormammalian target of rapamycinoxythiaminephosphatidylinositol 3 kinaseprotein kinase bprotein mdm2protein p53reactive oxygen metaboliteresveratrolritonavirtetrahydrolipstatintln 232unclassified drugaerobic glycolysisamino acid metabolismapoptosisautophagycell fatecell growthcell metabolismcitric acid cycledrug targetingenzyme regulationgene expression regulationglucose metabolismhumanintracellular signalingionizing radiationkidney metastasislipid metabolismliver cancermalignant neoplasmmelanomametabolic regulationmetabolismmyelomaosteosarcomaoxidative phosphorylationprotein dna bindingprotein functionprotein metabolismprotein phosphorylationreviewsenescencethyroid cancertranscription regulationtumor microenvironmentarticleCopyright IMPACT JOURNALS LLC10.18632/oncotarget.25267