Wednesday, January 27, 2016
Disregulated metabolism in cancer
I promise I'm not changing the title of this blog to "Metabolomics Research", but I'm kind of obsessed with the metabolome right now and I have limited reading time...so....
Today's breakfast paper is this review from MD Hirschey et al., and has 21 authors, every one of which appears to be at a different institution (Open Access). They're all members of the Halifax Project. Does this sound like an XMen story arc to you? It might to this group as well, cause you can find them at www.gettingtoknowcancer.org which seems a lot less ominous.
The goal of the HALIFAX PROJECT is to address the problems intrinsic to cancer heterogeneity (most cancer cells are cancerous for completely different reasons). One way to address it is to find common denominators. The first appears to be that their metabolomes are all screwed up.
This isn't new information. According to the review, excessive lactate formation was first detected in tumors almost 100 years ago and lots of work was done that indicated that glycolysis, amino acid synthesis and degradation, lipid metabolism and single carbon metabolism (among others) are messed up in tumors.
Interesting facts that pop out to me after going through this:
Tumors consume so much oxygen that there is often fermentation occurring in them. Even though fermentation produces only 5% as much ATP as glycolysis, ATP is not found to be limiting in tumors(!?!?)
Cancers revert to a bunch of different nutrient sources to maintain growth. For one they break down a lot of available lipids. Limiting fatty acid availability might be a cool cancer therapy
There are clinical trials in effect where the combination of calorie restriction and chemotherapy are being used to both limit the side effects of the therapeutics and to increase the efficacy of the drugs.
Since a ton of metabolism in humans is dependent on the mitochondria, focused treatments on those little buggers might be a strategy for moving forward.
There are serious links between having a messed up metabolism and having functional epigenetics. On top of the consequences of cells using up too many nutrients, producing too many toxic byproducts, now you've got proteins with weird PTMs and messed up histones? They mention in the paper that real targeted metabolic therapies for cancer are a ways off, but sure sounds like something I'm glad people are spending time on!