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Metabolic targets for potential prostate cancer therapeutics

机译:潜在的前列腺癌治疗药物的代谢目标

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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.
机译:审查目的前列腺癌(PCa)在从良性组织向恶性组织的转变过程中表现出新陈代谢和生物能的特征性变化。这些改变中的一些对于治疗目的是可靶向的是可行的。这篇综述将重点介绍目前正在研究的一些针对前列腺癌的代谢靶向疗法。最近的发现从良性到恶性的前列腺细胞的转变的特征是细胞内锌浓度降低,随后释放出三羧酸循环酶间-α-固溶酶抑制作用,这会导致癌症组织中柠檬酸盐的浓度降低。与大多数癌症所表现出的大部分糖酵解表型不同,PCa依靠谷氨酰胺和脂质来生存和增殖。早期研究开始证明,通过线粒体中的关键酶抑制剂(例如谷氨酰胺酶,脂肪酸合酶,3-羟基-3-甲基戊二酰辅酶A还原酶,己糖激酶,锌转运或复合物I)靶向某些上调的途径可能具有重要的代谢作用和治疗潜力。总结PCa独特的代谢谱可提供许多潜在的治疗途径。未来的研究将继续测试PCa的代谢特征和治疗是否可能是为疾病提供个性化治疗的重要方法。

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