Title | Metabolic alterations and targeted therapies in prostate cancer. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Flavin R, Zadra G, Loda M |
Journal | J Pathol |
Volume | 223 |
Issue | 2 |
Pagination | 283-94 |
Date Published | 2011 Jan |
ISSN | 1096-9896 |
Keywords | AMP-Activated Protein Kinases, Antineoplastic Agents, Enzyme Activators, Fatty Acid Synthases, Humans, Lipogenesis, Male, Prognosis, Prostatic Neoplasms, Signal Transduction |
Abstract | Cancer cells synthesize de novo large amounts of fatty acids and cholesterol, irrespective of the circulating lipid levels and benefit from this increased lipid synthesis in terms of growth advantage, self-survival and drug resistance. Key lipogenic alterations that commonly occur in prostate cancer include over-expression of the enzyme fatty acid synthase (FASN) and deregulation of the 5-AMP-activated protein kinase (AMPK). FASN is a key metabolic enzyme that catalyses the synthesis of palmitate from the condensation of malonyl-CoA and acetyl-CoA de novo and plays a central role in energy homeostasis, by converting excess carbon intake into fatty acids for storage. AMPK functions as a central metabolic switch that governs glucose and lipid metabolism. Recent interest has focused on the potential of targeting metabolic pathways that may be altered during prostate tumorigenesis and progression. Several small molecule inhibitors of FASN have now been described or in development for therapeutic use; in addition, drugs that directly or indirectly induce AMPK activation have potential benefit in prostate cancer prevention and treatment. |
DOI | 10.1002/path.2809 |
Alternate Journal | J Pathol |
PubMed ID | 21125681 |
Grant List | P01CA89021 / CA / NCI NIH HHS / United States R01CA131945 / CA / NCI NIH HHS / United States P50CA90381 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.