Kishton Rigel J, Rathmell Jeffrey C
From the Departments of *Pharmacology and Cancer Biology and †Immunology and ‡Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC.
Cancer J. 2015 Mar-Apr;21(2):62-9. doi: 10.1097/PPO.0000000000000099.
The study of tumor metabolism has resulted in new understandings of how cancer cells modify metabolic pathways that control cellular energetics to allow increased proliferation and survival. Tumor cells have been shown to alter metabolic pathways involved in glucose, glutamine, and mitochondrial metabolism to generate raw materials needed for rapid cellular proliferation, maintain favorable cellular redox environments, modify cellular epigenetics, and even promote and maintain oncogenic transformation. As a consequence, there has been intense scientific and clinical interest in targeting metabolic alterations that are commonly adopted by tumor cells for therapeutic purposes. In this review, we describe common metabolic alterations seen in tumor cells and discuss how these alterations are being investigated as potential targets for pharmacological intervention in preclinical and clinical settings. We also discuss some of the challenges associated with using tumor metabolism as a therapeutic target in cancer therapy, along with potential avenues to overcome these challenges.
肿瘤代谢研究使人们对癌细胞如何改变控制细胞能量的代谢途径以实现增殖和存活增加有了新的认识。研究表明,肿瘤细胞会改变参与葡萄糖、谷氨酰胺和线粒体代谢的途径,以生成细胞快速增殖所需的原料,维持有利的细胞氧化还原环境,改变细胞表观遗传学,甚至促进和维持致癌转化。因此,针对肿瘤细胞普遍采用的代谢改变进行治疗的研究引起了科学界和临床界的浓厚兴趣。在本综述中,我们描述了肿瘤细胞中常见的代谢改变,并讨论了如何在临床前和临床环境中将这些改变作为药物干预的潜在靶点进行研究。我们还讨论了将肿瘤代谢作为癌症治疗靶点所面临的一些挑战,以及克服这些挑战的潜在途径。