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恶性肿瘤的代谢靶向:一种系统方法的必要性。

Metabolic targeting of malignant tumors: a need for systemic approach.

作者信息

Margetis Aggelos T

机构信息

Internal Medicine-Oncology Residency Program, 2nd Department of Internal Medicine, Athens Naval and Veterans Hospital, 11521, Athens, Greece.

出版信息

J Cancer Res Clin Oncol. 2023 May;149(5):2115-2138. doi: 10.1007/s00432-022-04212-w. Epub 2022 Aug 4.

Abstract

PURPOSE

Dysregulated metabolism is now recognized as a fundamental hallmark of carcinogenesis inducing aggressive features and additional hallmarks. In this review, well-established metabolic changes displayed by tumors are highlighted in a comprehensive manner and corresponding therapeutical targets are discussed to set up a framework for integrating basic research findings with clinical translation in oncology setting.

METHODS

Recent manuscripts of high research impact and relevant to the field from PubMed (2000-2021) have been reviewed for this article.

RESULTS

Metabolic pathway disruption during tumor evolution is a dynamic process potentiating cell survival, dormancy, proliferation and invasion even under dismal conditions. Apart from cancer cells, though, tumor microenvironment has an acting role as extracellular metabolites, pH alterations and stromal cells reciprocally interact with malignant cells, ultimately dictating tumor-promoting responses, disabling anti-tumor immunity and promoting resistance to treatments.

CONCLUSION

In the field of cancer metabolism, there are several emerging prognostic and therapeutic targets either in the form of gene expression, enzyme activity or metabolites which could be exploited for clinical purposes; both standard-of-care and novel treatments may be evaluated in the context of metabolism rewiring and indeed, synergistic effects between metabolism-targeting and other therapies would be an attractive perspective for further research.

摘要

目的

代谢失调现已被视为致癌作用的一个基本特征,可诱导侵袭性特征及其他特征。在本综述中,全面突出了肿瘤所呈现的已确立的代谢变化,并讨论了相应的治疗靶点,以建立一个将基础研究成果与肿瘤学临床转化相结合的框架。

方法

本文对PubMed(2000 - 2021年)中近期具有高研究影响力且与该领域相关的手稿进行了综述。

结果

肿瘤演变过程中的代谢途径破坏是一个动态过程,即使在恶劣条件下也能增强细胞存活、休眠、增殖和侵袭能力。然而,除癌细胞外,肿瘤微环境也发挥作用,因为细胞外代谢产物、pH改变和基质细胞与恶性细胞相互作用,最终决定促肿瘤反应、抑制抗肿瘤免疫并促进对治疗的抵抗。

结论

在癌症代谢领域,存在几个以基因表达、酶活性或代谢产物形式出现的新兴预后和治疗靶点,可用于临床目的;在代谢重编程的背景下可评估标准治疗和新治疗方法,实际上,代谢靶向治疗与其他疗法之间的协同效应将是进一步研究的一个有吸引力的方向。

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