干预代谢途径在治疗肿瘤生长方面有极大优势，因为所有癌症实体都需要大量能量来支持生长所需的生物产物的生成。代谢癌症治疗的一个主要障碍是癌细胞（及其微环境）的代谢适应性和可塑性，导致治疗抵抗和逃逸。因此，代谢组合疗法非常有前景，因为它们旨在同时瞄准几条能量途径，并因此减少可用替代底物的数量。因此，可以结合饮食限制、特定营养素限制和/或药理干预来影响代谢途径，以提高癌症治疗效果，克服治疗抵抗，甚至作为一种预防措施。在这里，我们审查了代谢组合疗法的最新发展，特别强调了体内协同效应和可用临床数据的报告。最后，我们确定该领域的挑战（代谢肿瘤异质性、免疫细胞相互作用、患者间可变性），并建议“代谢类型”策略来根据肿瘤的能量需求以及患者的营养习惯和状态定制基于证据的代谢组合治疗。 版权所有© 2022 Elsevier Inc.。保留所有权利。

Therapeutically interfering with metabolic pathways has great merit to curtail tumor growth because the demand for copious amounts of energy for growth-supporting biomass production is common to all cancer entities. A major impediment to a straight implementation of metabolic cancer therapy is the metabolic flexibility and plasticity of cancer cells (and their microenvironment) resulting in therapy resistance and evasion. Metabolic combination therapies, therefore, are promising as they are designed to target several energetic routes simultaneously and thereby diminish the availability of alternative substrates. Thus, dietary restrictions, specific nutrient limitations, and/or pharmacological interventions impinging on metabolic pathways can be combined to improve cancer treatment efficacy, to overcome therapy resistance, or even act as a preventive measure. Here, we review the most recent developments in metabolic combination therapies particularly highlighting in vivo reports of synergistic effects and available clinical data. We close with identifying the challenges of the field (metabolic tumor heterogeneity, immune cell interactions, inter-patient variabilities) and suggest a "metabo-typing" strategy to tailor evidence-based metabolic combination therapies to the energetic requirements of the tumors and the patient's nutritional habits and status.Copyright © 2022 Elsevier Inc. All rights reserved.