Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA.
Adv Exp Med Biol. 2021;1311:229-248. doi: 10.1007/978-3-030-65768-0_17.
Despite the many recent breakthroughs in cancer research, oncology has traditionally been seen as a distinct field from other diseases. Recently, more attention has been paid to repurposing established therapeutic strategies and targets of other diseases towards cancer treatment, with some of these attempts generating promising outcomes [1, 2]. Recent studies using advanced metabolomics technologies [3] have shown evidence of close metabolic similarities between cancer and neurological diseases. These studies have unveiled several metabolic characteristics shared by these two categories of diseases, including metabolism of glutamine, gamma-aminobutyric acid (GABA), and N-acetyl-aspartyl-glutamate (NAAG) [4-6]. The striking metabolic overlap between cancer and neurological diseases sheds light on novel therapeutic strategies for cancer treatment. For example, 2-(phosphonomethyl) pentanedioic acid (2-PMPA), one of the glutamate carboxypeptidase II (GCP II) inhibitors that prevent the conversion of NAAG to glutamate, has been shown to suppress cancer growth [6, 7]. These promising results have led to an increased interest in integrating this metabolic overlap between cancer and neurological diseases into the study of cancer metabolism. The advantages of studying this metabolic overlap include not only drug repurposing but also translating existing knowledge from neurological diseases to the field of cancer research. This chapter discusses the specific overlapping metabolic features between cancer and neurological diseases, focusing on glutamine, GABA, and NAAG metabolisms. Understanding the interconnections between cancer and neurological diseases will guide researchers and clinicians to find more effective cancer treatments.
尽管癌症研究近年来取得了许多突破，但肿瘤学传统上被视为与其他疾病不同的领域。最近，人们越来越关注重新利用其他疾病的既定治疗策略和靶点来治疗癌症，其中一些尝试取得了有希望的结果[1,2]。最近使用先进代谢组学技术[3]的研究表明，癌症和神经疾病之间存在密切的代谢相似性。这些研究揭示了这两类疾病之间存在几种共同的代谢特征，包括谷氨酰胺、γ-氨基丁酸（GABA）和 N-乙酰天冬氨酸谷氨酸盐（NAAG）的代谢[4-6]。癌症和神经疾病之间惊人的代谢重叠揭示了癌症治疗的新治疗策略。例如，2-(膦酸甲基)戊二酸（2-PMPA）是一种谷氨酸羧肽酶 II（GCP II）抑制剂，可防止 NAAG 转化为谷氨酸，已被证明可抑制癌症生长[6,7]。这些有希望的结果导致人们越来越感兴趣地将癌症和神经疾病之间的这种代谢重叠纳入癌症代谢研究中。研究这种代谢重叠的优势不仅在于药物再利用，还在于将神经疾病的现有知识转化为癌症研究领域。本章讨论了癌症和神经疾病之间特定的重叠代谢特征，重点是谷氨酰胺、GABA 和 NAAG 代谢。了解癌症和神经疾病之间的相互联系将指导研究人员和临床医生找到更有效的癌症治疗方法。
