title: New strategies in prostate cancer: targeting lipogenic pathways and the energy sensor AMPK.
abstract: Although the role of metabolic syndrome (MS) and a high fat diet in prostate cancer (PCa) risk is still a matter of intense debate, it is becoming increasingly clear that obesity can cause perturbations in metabolic pathways that contribute to the pathogenesis and progression of PCa. Moreover, prostate epithelial cells per se undergo a series of metabolic changes, including an increase in de novo lipogenesis, during the process of tumor formation. These metabolic alterations, at both the cellular and organismal levels, are intertwined with genetic aberrations necessary for neoplastic transformation. Thus, altered metabolism is currently subject to intense research efforts and might provide preventative and therapeutic opportunities, as well as a platform for biomarker development. In this article, we review evidence that the metabolic sensor 5'-AMP-activated protein kinase (AMPK), which physiologically integrates nutritional and hormonal signals and regulates cell survival and growth-related metabolic pathways to preserve intracellular ATP levels, represents a link between energy homeostasis and cancer. Thus, when AMPK is not activated, as in the setting of MS and obesity, systemic metabolic alterations permissive to the development of PCa are allowed to proceed unchecked. Hence, the use of AMPK activators and inhibitors of key lipogenic enzymes may represent a promising therapeutic strategy for PCa.
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Zadra
authors.forename: Carmen
authors.initials: C
authors.lastname: Priolo
authors.forename: Akash
authors.initials: A
authors.lastname: Patnaik
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D004041:Dietary Fats; D004734:Energy Metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications; D009765:Obesity / Q000150:complications; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D004041:Dietary Fats; D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases