Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer.
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ABSTRACT:
SUBMITTER: Lord SR
PROVIDER: S-EPMC6224605 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer.
Lord Simon R SR Cheng Wei-Chen WC Liu Dan D Gaude Edoardo E Haider Syed S Metcalf Tom T Patel Neel N Teoh Eugene J EJ Gleeson Fergus F Bradley Kevin K Wigfield Simon S Zois Christos C McGowan Daniel R DR Ah-See Mei-Lin ML Thompson Alastair M AM Sharma Anand A Bidaut Luc L Pollak Michael M Roy Pankaj G PG Karpe Fredrik F James Tim T English Ruth R Adams Rosie F RF Campo Leticia L Ayers Lisa L Snell Cameron C Roxanis Ioannis I Frezza Christian C Fenwick John D JD Buffa Francesca M FM Harris Adrian L AL
Cell metabolism 20180920 5
Late-phase clinical trials investigating metformin as a cancer therapy are underway. However, there remains controversy as to the mode of action of metformin in tumors at clinical doses. We conducted a clinical study integrating measurement of markers of systemic metabolism, dynamic FDG-PET-CT, transcriptomics, and metabolomics at paired time points to profile the bioactivity of metformin in primary breast cancer. We show metformin reduces the levels of mitochondrial metabolites, activates multi ...[more]
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