PHARMACO-METABOLOMICS FOR ANTICANCER DRUGS

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Abstract

Metabolomics is a biochemical phenotype of cellular events after gene expression, transcription and translation, and recently it has been included as a new ‘omics’ science, as a new field toward the understanding of global system biology. Since there are numerous networks with thousands of metabolites in human cells, a key technology for metabolomics is the separation analysis of these abundant metabolites. The mass spectrometry (MS) plays a central role for identification and quantification of metabolites in biological fluids. LC-MS is useful for studying hydrophobic metabolites, while the capillary electrophoresis (CE)-MS is a powerful method for analyzing charged compounds such as weak anions and cations.

Cancer metabolomics is an emerging field in cancer biology. Cancer-specific metabolic reprogramming such as the Warburg effect is considered to facilitate cell growth and division. Several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass, rather than ATP production.

We have firstly applied the CE-TOFMS metabolomic analysis to the pharmacology. Pharmaco-metabolomics investigates the drug action on the global metabolomic profiling and pathways. A comprehensive metabolomic fingerprint of cancer cells is expected to differentiate response or non-response to the drug therapy. Our recent findings regarding two metabolic inhibitors (5-FU and gemcitabine) are presented as examples. The metabolomic analyses can create new findings on cancer biology, pharmacology as well as potential biomarkers for drug action in the post-genome era.

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