TY - JOUR
T1 - Metabolomics, metabolic flux analysis and cancer pharmacology
AU - Liang, Lingfan
AU - Sun, Fei
AU - Wang, Hongbo
AU - Hu, Zeping
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - cancer
KW - drug discovery
KW - metabolic flux
KW - metabolomics
KW - pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85102245160&partnerID=8YFLogxK
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U2 - 10.1016/j.pharmthera.2021.107827
DO - 10.1016/j.pharmthera.2021.107827
M3 - Review article
C2 - 33662451
AN - SCOPUS:85102245160
SN - 0163-7258
VL - 224
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
M1 - 107827
ER -