Metabolomics, metabolic flux analysis and cancer pharmacology

Metabolic reprogramming is a hallmark of cancer and increasing evidence suggests that reprogrammed cell metabolism supports tumor initiation, progression, metastasis and drug resistance. Understanding metabolic dysregulation may provide therapeutic targets and facilitate drug research and developmen...

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Published inPharmacology & therapeutics (Oxford) Vol. 224; p. 107827
Main Authors Liang, Lingfan, Sun, Fei, Wang, Hongbo, Hu, Zeping
Format Journal Article
LanguageEnglish
Published England Elsevier Inc 01.08.2021
Subjects
cancer
drug discovery
Humans
metabolic flux
Metabolic Flux Analysis
Metabolomics
Neoplasms - drug therapy
pharmacology
cancer
drug discovery
metabolomics
metabolic flux
pharmacology
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Abstract Metabolic reprogramming is a hallmark of cancer and increasing evidence suggests that reprogrammed cell metabolism supports tumor initiation, progression, metastasis and drug resistance. Understanding metabolic dysregulation may provide therapeutic targets and facilitate drug research and development for cancer therapy. Metabolomics enables the high-throughput characterization of a large scale of small molecule metabolites in cells, tissues and biofluids, while metabolic flux analysis (MFA) tracks dynamic metabolic activities using stable isotope tracer methods. Recent advances in metabolomics and MFA technologies make them powerful tools for metabolic profiling and characterizing metabolic activities in health and disease, especially in cancer research. In this review, we introduce recent advances in metabolomics and MFA analytical technologies, and provide the first comprehensive summary of the most commonly used isotope tracing methods. In addition, we highlight how metabolomics and MFA are applied in cancer pharmacology studies particularly for discovering targetable metabolic vulnerabilities, understanding the mechanisms of drug action and drug resistance, exploring potential strategies with dietary intervention, identifying cancer biomarkers, as well as enabling precision treatment with pharmacometabolomics.
AbstractList Metabolic reprogramming is a hallmark of cancer and increasing evidence suggests that reprogrammed cell metabolism supports tumor initiation, progression, metastasis and drug resistance. Understanding metabolic dysregulation may provide therapeutic targets and facilitate drug research and development for cancer therapy. Metabolomics enables the high-throughput characterization of a large scale of small molecule metabolites in cells, tissues and biofluids, while metabolic flux analysis (MFA) tracks dynamic metabolic activities using stable isotope tracer methods. Recent advances in metabolomics and MFA technologies make them powerful tools for metabolic profiling and characterizing metabolic activities in health and disease, especially in cancer research. In this review, we introduce recent advances in metabolomics and MFA analytical technologies, and provide the first comprehensive summary of the most commonly used isotope tracing methods. In addition, we highlight how metabolomics and MFA are applied in cancer pharmacology studies particularly for discovering targetable metabolic vulnerabilities, understanding the mechanisms of drug action and drug resistance, exploring potential strategies with dietary intervention, identifying cancer biomarkers, as well as enabling precision treatment with pharmacometabolomics.Metabolic reprogramming is a hallmark of cancer and increasing evidence suggests that reprogrammed cell metabolism supports tumor initiation, progression, metastasis and drug resistance. Understanding metabolic dysregulation may provide therapeutic targets and facilitate drug research and development for cancer therapy. Metabolomics enables the high-throughput characterization of a large scale of small molecule metabolites in cells, tissues and biofluids, while metabolic flux analysis (MFA) tracks dynamic metabolic activities using stable isotope tracer methods. Recent advances in metabolomics and MFA technologies make them powerful tools for metabolic profiling and characterizing metabolic activities in health and disease, especially in cancer research. In this review, we introduce recent advances in metabolomics and MFA analytical technologies, and provide the first comprehensive summary of the most commonly used isotope tracing methods. In addition, we highlight how metabolomics and MFA are applied in cancer pharmacology studies particularly for discovering targetable metabolic vulnerabilities, understanding the mechanisms of drug action and drug resistance, exploring potential strategies with dietary intervention, identifying cancer biomarkers, as well as enabling precision treatment with pharmacometabolomics.
Metabolic reprogramming is a hallmark of cancer and increasing evidence suggests that reprogrammed cell metabolism supports tumor initiation, progression, metastasis and drug resistance. Understanding metabolic dysregulation may provide therapeutic targets and facilitate drug research and development for cancer therapy. Metabolomics enables the high-throughput characterization of a large scale of small molecule metabolites in cells, tissues and biofluids, while metabolic flux analysis (MFA) tracks dynamic metabolic activities using stable isotope tracer methods. Recent advances in metabolomics and MFA technologies make them powerful tools for metabolic profiling and characterizing metabolic activities in health and disease, especially in cancer research. In this review, we introduce recent advances in metabolomics and MFA analytical technologies, and provide the first comprehensive summary of the most commonly used isotope tracing methods. In addition, we highlight how metabolomics and MFA are applied in cancer pharmacology studies particularly for discovering targetable metabolic vulnerabilities, understanding the mechanisms of drug action and drug resistance, exploring potential strategies with dietary intervention, identifying cancer biomarkers, as well as enabling precision treatment with pharmacometabolomics.
ArticleNumber 107827
Author Liang, Lingfan
Sun, Fei
Wang, Hongbo
Hu, Zeping
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  givenname: Hongbo
  surname: Wang
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  email: hongbowang@ytu.edu.cn
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  givenname: Zeping
  surname: Hu
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  email: zeping_hu@tsinghua.edu.cn
  organization: School of Pharmaceutical Sciences; Tsinghua-Peking Joint Center for Life Sciences; Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing 100084, China
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Keywords cancer
drug discovery
metabolomics
metabolic flux
pharmacology
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Snippet Metabolic reprogramming is a hallmark of cancer and increasing evidence suggests that reprogrammed cell metabolism supports tumor initiation, progression,...
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SubjectTerms cancer
drug discovery
Humans
metabolic flux
Metabolic Flux Analysis
Metabolomics
Neoplasms - drug therapy
pharmacology
Title Metabolomics, metabolic flux analysis and cancer pharmacology
URI https://dx.doi.org/10.1016/j.pharmthera.2021.107827
https://www.ncbi.nlm.nih.gov/pubmed/33662451
https://www.proquest.com/docview/2498503652
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