Metabolic targets for potential prostate cancer therapeutics

被引:32
作者
Twum-Ampofo, Jeffrey [1 ,2 ]
Fu, De-Xue [1 ]
Passaniti, Antonino [3 ,4 ,5 ,6 ]
Hussain, Arif [4 ,5 ,6 ]
Siddiqui, M. Minhaj [1 ,5 ,6 ]
机构
[1] Univ Maryland, Div Urol, Dept Surg, Sch Med, 29 S Greene St Suite 500, Baltimore, MD 21044 USA
[2] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA
[3] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA
[4] Univ Maryland, Dept Biochem & Mol Biol, Sch Med, Baltimore, MD 21201 USA
[5] Univ Maryland, Vet Hlth Adm Res & Dev Serv, Sch Med, Baltimore, MD 21201 USA
[6] Univ Maryland, Greenebaum Canc Ctr, Sch Med, Baltimore, MD 21201 USA
关键词
investigational; metabolic networks and pathways; metabolism; metabolomics; precision medicine; prostatic neoplasms; therapies; FATTY-ACID SYNTHASE; PROTEIN-KINASE ACTIVATORS; CITRATE METABOLISM; BREAST-CANCER; ZINC; CELLS; EXPRESSION; SORAFENIB; DIET; INHIBITION;
D O I
10.1097/CCO.0000000000000276
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose of reviewProstate cancer (PCa) demonstrates characteristic changes in metabolism and bioenergetics in the transition from benign to malignant tissue. It is feasible that some of these changes may be targetable for therapeutic purposes. This review will highlight some of the current metabolically targeted therapies being investigated for the treatment of prostate cancer.Recent findingsThe transition from benign to malignant prostate cells is characterized by decreased intracellular zinc concentration and subsequent release of inhibition of the tricarboxylic acid cycle enzyme m-aconitase, which leads to the decrease in citrate concentration within the cancer tissue. Instead of the largely glycolytic phenotype exhibited by most cancers, PCa relies on glutamine and lipids for survival and proliferation. Early studies are beginning to demonstrate that targeting some of the upregulated pathways with inhibitors of key enzymes, such as glutaminase, fatty acid synthase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, hexokinase, zinc transport, or complex I in the mitochondria may have significant metabolic effects and therapeutic potential.SummaryThe unique metabolic profile of PCa allows for many potential avenues of treatment. Future studies will continue to test if the metabolic characterization and treatment of PCa could be an important approach to provide personalized treatment for the disease.
引用
收藏
页码:241 / 247
页数:7
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