Metabolic modulation of cancer: a new frontier with great translational potential

Verfasser / Beitragende:
[Adam Kinnaird, Evangelos Michelakis]
Ort, Verlag, Jahr:
2015
Enthalten in:
Journal of Molecular Medicine, 93/2(2015-02-01), 127-142
Format:
Artikel (online)
ID: 605543925
LEADER caa a22 4500
001 605543925
003 CHVBK
005 20210128100929.0
007 cr unu---uuuuu
008 210128e20150201xx s 000 0 eng
024 7 0 |a 10.1007/s00109-014-1250-2  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00109-014-1250-2 
245 0 0 |a Metabolic modulation of cancer: a new frontier with great translational potential  |h [Elektronische Daten]  |c [Adam Kinnaird, Evangelos Michelakis] 
520 3 |a Metabolic oncology is an exciting new field in cancer research, offering a new window to cancer's molecular plasticity and promise for the development of effective, cancer-selective therapies and novel biomarkers. It is based on the realization that cancer's unique metabolism (known since Warburg's report in 1923) with suppression of mitochondrial glucose oxidation and upregulation of cytoplasmic glycolysis is not a secondary but a primary event, offering many growth advantages to cancer cells. Many mechanisms have been revealed, including growth factors, oncogenes, and mutations, all contributing to a suppression of mitochondria, similar to what takes place in hypoxia. This suppression leads to inhibition of mitochondria-driven apoptosis, promotes proliferation, and enhances angiogenesis and metastatic potential. A number of molecular tools and small molecules targeting metabolic enzymes, including pyruvate kinase, pyruvate dehydrogenase kinase, isocitrate dehydrogenase, and lactate dehydrogenase, have been developed, inhibiting cancer growth in vitro and in vivo in several cancer types. Several have already entered early-phase trials, a great translational success considering the young age of the field (less than 10years). Here we review the mechanisms and effects of these metabolic modulators and the rationale for further development. This rapidly accumulating knowledge allows some optimism that this may prove to be a paradigm shift in the way we understand and treat cancer. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Metabolic oncology  |2 nationallicence 
690 7 |a Cancer metabolism  |2 nationallicence 
690 7 |a Mitochondria  |2 nationallicence 
700 1 |a Kinnaird  |D Adam  |u Department of Medicine, University of Alberta, T6G 2B7, Edmonton, AB, Canada  |4 aut 
700 1 |a Michelakis  |D Evangelos  |u Department of Medicine, University of Alberta, T6G 2B7, Edmonton, AB, Canada  |4 aut 
773 0 |t Journal of Molecular Medicine  |d Springer Berlin Heidelberg  |g 93/2(2015-02-01), 127-142  |x 0946-2716  |q 93:2<127  |1 2015  |2 93  |o 109 
856 4 0 |u https://doi.org/10.1007/s00109-014-1250-2  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a review-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00109-014-1250-2  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kinnaird  |D Adam  |u Department of Medicine, University of Alberta, T6G 2B7, Edmonton, AB, Canada  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Michelakis  |D Evangelos  |u Department of Medicine, University of Alberta, T6G 2B7, Edmonton, AB, Canada  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Journal of Molecular Medicine  |d Springer Berlin Heidelberg  |g 93/2(2015-02-01), 127-142  |x 0946-2716  |q 93:2<127  |1 2015  |2 93  |o 109