Metabolic Reprogramming in Human Cancer Patients and Patient-Derived Models.

IF 7.8 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-15 DOI:10.1101/cshperspect.a041552
Teresa W-M Fan, Richard M Higashi, Andrew N Lane
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Abstract

Stable isotope-resolved metabolomics delineates reprogrammed intersecting metabolic networks in human cancers. Knowledge gained from in vivo patient studies provides the "benchmark" for cancer models to recapitulate. It is particularly difficult to model patients' tumor microenvironment (TME) with its complex cell-cell/cell-matrix interactions, which shapes metabolic reprogramming crucial to cancer development/drug resistance. Patient-derived organotypic tissue cultures (PD-OTCs) represent a unique model that retains an individual patient's TME. PD-OTCs of non-small-cell lung cancer better recapitulated the in vivo metabolic reprogramming of patient tumors than the patient-derived tumor xenograft (PDTX), while enabling interrogation of immunometabolic response to modulators and TME-dependent resistance development. Patient-derived organoids (PDOs) are also good models for reconstituting TME-dependent metabolic reprogramming and for evaluating therapeutic responses. Single-cell based 'omics on combinations of PD-OTC and PDO models will afford an unprecedented understanding on TME dependence of human cancer metabolic reprogramming, which should translate into the identification of novel metabolic targets for regulating TME interactions and drug resistance.

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人类癌症患者和患者衍生模型的代谢重编程。
稳定同位素分辨代谢组学描绘了人类癌症中重新编程的交叉代谢网络。从患者体内研究中获得的知识为癌症模型的再现提供了 "基准"。患者的肿瘤微环境(TME)具有复杂的细胞-细胞/细胞-基质相互作用,对癌症发展/耐药性至关重要,因此要模拟患者的肿瘤微环境尤其困难。患者来源的器官型组织培养物(PD-OTCs)是一种独特的模型,它保留了患者个体的肿瘤微环境。与患者来源肿瘤异种移植(PDTX)相比,非小细胞肺癌的患者来源器官型组织培养物能更好地再现患者肿瘤在体内的代谢重编程,同时还能检测免疫代谢对调节剂的反应以及TME依赖的抗药性发展。患者来源的器官组织(PDOs)也是重建依赖于TME的代谢重编程和评估治疗反应的良好模型。基于单细胞的'omics'研究结合 PD-OTC 和 PDO 模型,将对人类癌症代谢重编程的 TME 依赖性有前所未有的了解,这将有助于确定调节 TME 相互作用和耐药性的新型代谢靶点。
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来源期刊
Cold Spring Harbor perspectives in medicine
Cold Spring Harbor perspectives in medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
14.30
自引率
1.90%
发文量
44
审稿时长
4-8 weeks
期刊介绍: Cold Spring Harbor Perspectives in Medicine is a monthly online publication comprising reviews on different aspects of a variety of diseases, covering everything from the molecular and cellular bases of disease to translational medicine and new therapeutic strategies. Cold Spring Harbor Perspectives in Medicine is thus unmatched in its depth of coverage and represents an essential source where readers can find informed surveys and critical discussion of advances in molecular medicine.
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