WOW! I know this is merely from models at this point and not clinic, but it seems this is a radical revelation if verified! Am I missing something or is this as revolutionary as it appears? Again, I know the scientific process has a long way to go, but the claim seems like a whole new world would be opened.
http://m.huffpost.com/uk/entry/uk_5774e95de4b08b8610d782bc?edition=uk
Grace and peace,
Danny
This isn't the first study to show something like this. A 2013 study from UCLA showed that radiation resistant glioma-cells had increased fatty acid oxidation with less reliance on glucose, and used etomoxir to inhibit FAO (fatty acid oxidation), the same drug mentioned in the Huff Post story.
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pubmed/24260384
I would not call this a case of either/or. Cancer cells are more adaptable than given credit for. Like normal cells they can use other energy sources if glucose is in short supply, or if they're under pressure in other ways, as in the 2013 study. Glucose is undoubtedly important, but not the only possible energy source as suggested by some authors.
The wikipedia article on etomoxir suggests this might not be a great new drug candidate: phase 2 trial of the drug for heart failure was terminated due to adverse side-effects and "the clinical development of etomoxir has been terminated due to severe hepatotoxicity associated with treatment".
Likewise cancer cells can be stimulated by protein. A person still needs to eat of course, as the body requires glucose, fatty acids and amino acids. This article does not overturn the idea that maintaining lowish blood glucose levels is still a good idea: Retrospective studies have shown a correlation with lower glucose levels and better prognosis, and vice-versa.
I've learned not to draw any conclusions whatsoever based on newspaper articles, which are often quite distorted in their facts, but to wait for the research to be published. The most recent article I could find for the Stoll group on pubmed was a 2015 article about neural stem cells and fatty acid oxidation.
http://www.ncbi.nlm.nih.gov/pubmed/25919237
The new study will be an interesting read when published, but may not be as revolutionary as the news article makes it out to be.
Also contrary to the dogma that has grown up around the ketogenic diet, at least some types of cancer cells can metabolize ketones for energy, just like normal cells:
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pubmed/27142056
This doesn't mean the ketogenic diet has no validity, just that it will probably work better for some than for others, and we could say the same about any therapy.
Looks like the study in question was published online yesterday in Neuro-Oncology, and so wasn't even on pubmed yet. Fortunately it's open access:
ReplyDeletehttp://neuro-oncology.oxfordjournals.org/content/early/2016/06/29/neuonc.now128.full
I'll be sure to comment on this after reading.
The study contributes to our knowledge by showing that primary glioma cell lines do make use of fatty acid oxidation as an energy source inside the mitochondria. However this does not negate the importance of glucose. This study was focused on oxygen consumption rates in the mitochondria, whereas the majority of glucose is converted to lactate outside the mitochondria. The real importance of glucose is not in terms of mitochondrial energy production (the focus of this study) but in providing a carbon substrate for macromolecular synthesis (being used as building blocks for new cellular materials as opposed to being broken down in the mitochondria for energy).
ReplyDeleteI see this study as a complement to our current knowledge, rather than a revolution that overturns the importance of glucose to cancer cells (which is kind of the spin that the news article gave it).
Administering etomoxir to glioma-bearing mice did increase survival somewhat (max survival ~110 days in the etomoxir group versus >80 days in the control group).
The study concludes by saying:
"Etomoxir has already been tested in phase I/II clinical trials for treating moderate congestive heart failure; this trial was discontinued because 4 patients (of 226 taking the drug) developed unacceptably high liver transaminase levels upon treatment,and the risk of such drastic side effects was deemed sufficient to negate the potential benefit of this drug for these patients. However, the treatment options and survival expectancy for patients with malignant glioma is much more dire, and the potential benefit in regard to risk is very different for patients with this diagnosis. This drug may therefore provide promise for clinical therapies aimed to slow the growth and progression of malignant glioma"
This is a good point, but whether the marginal increase in survival seen in the mice would translate to humans is unknown - perhaps a trial will be carried out at some point. Etomoxir is not an approved drug, so couldn't be added as an off-label prescription the way we're doing with approved drugs.
If we're talking mouse studies and diets, the most impressive study yet published was the combination of ketogenic diet + radiation, which apparently cured a majority of glioma-bearing mice thus treated. A study of etomoxir + radiation would be very interesting in this context.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341352/
Edit to the above comment: glucose has multiple, non-mitochondrial uses in proliferating cells. Downstream metabolites of glucose can be used as building blocks for the synthesis of nucleotides, lipids, as well as other uses. Lactate is only one of the many fates of glucose in proliferating cells. And like the fatty acids in the study under discussion glucose can also be oxidized in the mitochondria, but this is not necessarily its most important function in proliferating cells.
ReplyDeleteReference:
Famine versus feast: understanding the metabolism of tumors in vivo
http://www.ncbi.nlm.nih.gov/pubmed/25639751
Thank you Stephen! So bottom line -- does it make sense to stay with the Keto diet?
ReplyDeleteGiven the current evidence, yes I think the keto diet could still be helpful. I've seen multiple mouse studies of ketogenic diet, and they usually show some degree of inhibition of tumor growth (I've never seen the opposite happen).
DeleteHowever, I would look into the modified ketogenic diet developed in Brent Reynolds lab at the University of Florida (first author R. Martuscello).
http://www.ncbi.nlm.nih.gov/pubmed/26631612 (I'll upload this study to the library if it's not there already)
The reason I suggest this is that the ratios are not as extreme as with the strict ketogenic diet, so it's easier to stick with it, but the survival prolongation in mice was identical compared with a strict ketogenic diet.
I'll add more details about this diet after I dig them up.