title: The fat side of prostate cancer.
abstract: Prostate cancer (PCa) metabolism appears to be unique in comparison with other types of solid cancers. Normal prostate cells mainly rely on glucose oxidation to provide precursors for the synthesis and secretion of citrate, resulting in an incomplete Krebs cycle and minimal oxidative phosphorylation for energy production. In contrast, during transformation, PCa cells no longer secrete citrate and they reactivate the Krebs cycle as energy source. Moreover, primary PCas do not show increased aerobic glycolysis and therefore they are not efficiently detectable with (18)F-FDG-PET. However, increased de novo lipid synthesis, strictly intertwined with deregulation in classical oncogenes and oncosuppressors, is an early event of the disease. Up-regulation and increased activity of lipogenic enzymes (including fatty acid synthase and choline kinase) occurs throughout PCa carcinogenesis and correlates with worse prognosis and poor survival. Thus, lipid precursors such as acetate and choline have been successfully used as alternative tracers for PET imaging. Lipid synthesis intermediates and FA catabolism also emerged as important players in PCa maintenance. Finally, epidemiologic studies suggested that systemic metabolic disorders including obesity, metabolic syndrome, and diabetes as well as hypercaloric and fat-rich diets might increase the risk of PCa. However, how metabolic disorders contribute to PCa development and whether dietary lipids and de novo lipids synthesized intra-tumor are differentially metabolized still remains unclear. In this review, we examine the switch in lipid metabolism supporting the development and progression of PCa and we discuss how we can exploit its lipogenic nature for therapeutic and diagnostic purposes. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Zadra
authors.forename: Cornelia
authors.initials: C
authors.lastname: Photopoulos
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
mesh_terms: D016147:Genes, Tumor Suppressor; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D009857:Oncogenes; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*
keywords: Fatty acids; Imaging; Lipid metabolism; Metabolic diseases; Prostate cancer
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