Francesca Giunchi1, Michelangelo Fiorentino2, Massimo Loda3. 1. Division of Genito-Urinary Pathology, S.Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy. 2. Division of Genito-Urinary Pathology, S.Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy. Electronic address: michelangelo.fiorentino@unibo.it. 3. Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Abstract
CONTEXT: Neoplastic cells are characterized by metabolic alterations that sustain tumor growth. Interventions aimed at modifying metabolic rewiring of cancer cells are currently being investigated in several tumor types, including prostate cancer (PC). OBJECTIVE: To review relevant metabolic alterations reported for PC and potential diagnostic and therapeutic opportunities that could be exploited on the basis of these discoveries. EVIDENCE ACQUISITION: We performed a review of PubMed/Medline in March 2018 for PC in association with each of the following search terms: metabolomics; lipid, cholesterol, one-carbon, amino acid, and glucose metabolism. Fifty publications were selected for inclusion in this analysis. EVIDENCE SYNTHESIS: The reports included were grouped according to fatty acid and cholesterol metabolism (28 studies); one-carbon metabolism (9 studies); amino acid metabolism (6 studies); and glucose metabolism (7 studies). We report on multiple metabolic pathways that are dysregulated in prostate cancer. Metabolic alterations can result in at least one of the following changes: protein lipidation, oncogene activation, DNA methylation, cellular signaling, and protein-protein interactions. CONCLUSIONS: Metabolic alterations play a crucial role in PC development, progression, and resistance to therapy. Increasing knowledge of metabolic rewiring is revealing novel metabolic signatures in PC. These signatures could be utilized for PC diagnosis, as well as for the discovery of novel therapeutic interventions to overcome castration resistance. PATIENT SUMMARY: Metabolic alterations play a crucial role in the development and progression of prostate cancer and its resistance to therapy. Our knowledge of metabolic rewiring is increasing and revealing novel metabolic signatures in prostate cancer. These signatures could be used for diagnosis and for the discovery of novel therapeutic interventions aimed at overcoming castration resistance.
CONTEXT: Neoplastic cells are characterized by metabolic alterations that sustain tumor growth. Interventions aimed at modifying metabolic rewiring of cancer cells are currently being investigated in several tumor types, including prostate cancer (PC). OBJECTIVE: To review relevant metabolic alterations reported for PC and potential diagnostic and therapeutic opportunities that could be exploited on the basis of these discoveries. EVIDENCE ACQUISITION: We performed a review of PubMed/Medline in March 2018 for PC in association with each of the following search terms: metabolomics; lipid, cholesterol, one-carbon, amino acid, and glucose metabolism. Fifty publications were selected for inclusion in this analysis. EVIDENCE SYNTHESIS: The reports included were grouped according to fatty acid and cholesterol metabolism (28 studies); one-carbon metabolism (9 studies); amino acid metabolism (6 studies); and glucose metabolism (7 studies). We report on multiple metabolic pathways that are dysregulated in prostate cancer. Metabolic alterations can result in at least one of the following changes: protein lipidation, oncogene activation, DNA methylation, cellular signaling, and protein-protein interactions. CONCLUSIONS: Metabolic alterations play a crucial role in PC development, progression, and resistance to therapy. Increasing knowledge of metabolic rewiring is revealing novel metabolic signatures in PC. These signatures could be utilized for PC diagnosis, as well as for the discovery of novel therapeutic interventions to overcome castration resistance. PATIENT SUMMARY: Metabolic alterations play a crucial role in the development and progression of prostate cancer and its resistance to therapy. Our knowledge of metabolic rewiring is increasing and revealing novel metabolic signatures in prostate cancer. These signatures could be used for diagnosis and for the discovery of novel therapeutic interventions aimed at overcoming castration resistance.
Authors: Eugenio Zoni; Martina Minoli; Cédric Bovet; Anne Wehrhan; Salvatore Piscuoglio; Charlotte K Y Ng; Peter C Gray; Martin Spahn; George N Thalmann; Marianna Kruithof-de Julio Journal: BMC Cancer Date: 2019-12-16 Impact factor: 4.430