دورية أكاديمية
Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer.
| العنوان: | Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer. |
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| المؤلفون: | Lord, SR, Cheng, W-C, Liu, D, Gaude, E, Haider, S, Metcalf, T, Patel, N, Teoh, EJ, Gleeson, F, Bradley, K, Wigfield, S, Zois, C, McGowan, DR, Ah-See, M-L, Thompson, AM, Sharma, A, Bidaut, L, Pollak, M, Roy, PG, Karpe, F, James, T, English, R, Adams, RF, Campo, L, Ayers, L, Snell, C, Roxanis, I, Frezza, C, Fenwick, JD, Buffa, FM, Harris, AL |
| المساهمون: | Haider, Syed |
| بيانات النشر: | CELL PRESS |
| سنة النشر: | 2021 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| مصطلحات موضوعية: | Mitochondria, Humans, Breast Neoplasms, Metformin, Glucose, Antineoplastic Agents, Hypoglycemic Agents, Gene Expression Regulation, Neoplastic, Adult, Aged, Middle Aged, Female, Metabolic Networks and Pathways, Transcriptome, Positron Emission Tomography Computed Tomography |
| الوصف: | 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 multiple mitochondrial metabolic pathways, and increases 18-FDG flux in tumors. Two tumor groups are identified with distinct metabolic responses, an OXPHOS transcriptional response (OTR) group for which there is an increase in OXPHOS gene transcription and an FDG response group with increased 18-FDG uptake. Increase in proliferation, as measured by a validated proliferation signature, suggested that patients in the OTR group were resistant to metformin treatment. We conclude that mitochondrial response to metformin in primary breast cancer may define anti-tumor effect. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; 688.e4; application/pdf |
| اللغة: | English |
| تدمد: | 1550-4131 1932-7420 |
| العلاقة: | Cell metabolism, 2018, 28 (5), pp. 679 - 688.e4; https://repository.icr.ac.uk/handle/internal/4626Test |
| DOI: | 10.1016/j.cmet.2018.08.021 |
| الإتاحة: | https://doi.org/10.1016/j.cmet.2018.08.021Test https://repository.icr.ac.uk/handle/internal/4626Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.5C42125F |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15504131 19327420 |
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| DOI: | 10.1016/j.cmet.2018.08.021 |