angiogenesis and Warburg Effect

I work in cancer research and of late I've been investigating the affects of some chemicals on angiogenesis, particularly as it relates to breast cancer. Now I'm a technician, not a PI, so my nose is to the ground and I often miss the big picture since my concerns are oriented towards the day-to-day research. As a result, I often get tunnel vision and only look at cancer through the prism of my research.

In this case that means that I frequently think of cancer as only developing when there's plenty of oxygen available--which is reasonable since as a fast dividing group of cells, a cancer tumor needs lots of energy which would seem to imply oxidative reduction, not glycolysis--which requires sufficient vascularization and thus angiogenesis.

However the cancer picture is more complex than that and the Warburg Effect is one example of that. Some tumors actually preferentially grow in the absence of oxygen and use glycolysis as their primary source of energy. They do this by blocking mitochondrial activity. Since the mitochondria have potential use in natural anticancer activity by inducting apoptosis in some circumstances this is a strategy that can be helpful to the long term survival of the cancer. Obviously for our health we'd like to reverse this and there's drug research going on that tries to target this biochemical pathway.

For example, by blocking the production of NAD, a chemical precursor to ATP, the cancerous cell will eventually die by apoptosis. This allows for the creation of chemotherapy drugs by targeting specific fast growing cells. Like with most chemotherapies, there's collateral damage to other tissues in the body but since most fast growing cells rely heavily on the mitochondria for their ATP production, which these drugs would not affect, the damage shouldn't be as bad as with more traditional chemotherapy. At least that's the theory. Since I work with angiogenesis drugs, these Warburg Effect oriented drugs are a mystery to me. I'm just starting to read up on them and how they work.

The figure to the left illustrates how the cells in the body generate energy which is stored in the form of the chemical bonds in ATP (adenosine tri phosphate). Glycolysis, which doesn't need oxygen, results in just 2 ATP molecules for every molecule of glucose catalyzed. The Krebs cycle, by way of contrast, which takes place in the mitochondria, generates 36 ATPs from every molecule of glucose. It generates excess carbon and oxygen is needed to carry the carbon away ultimately in the form of CO2 and water. The illustration shows the end "waste" result as being HCO3 but that's just an interim product:

2 * HCO3 ----> H2O + 2 * CO2

There's one extra oxygen atom left over up there. Damn. Chemistry. You gotta love it. Anybody need an extra oxygen atom?


kenju said…
Well, Dave, there's at least ONE good reason I never took chemistry!! (too dumb)

I did screen Pap smears and breast cancer slides, though, so this is interesting even if I didn't understand all of it. A woman fairly close to me is undergoing chemo at present, so I am understandably interested.

BTW: she had a shot (only one) before starting chemo that is supposed to help with the after-effects (esp. nausea). Guess how much it costs?
Anonymous said…
This bought my A Level Biology flooding back adn was very interesting.

I also did chemistry and remember many fun hours of balancing equations. Seems I often had an extra atom or so left over too!
Anonymous said…
Oops - forgot to say that Michele sent me this time.
kenju said…
Michele sent me back, Dave. How is your sunny Sat?
Surcie said…
Just dropping by to tell you that your comment re: my box was hilarious!
Anonymous said…
I know what you mean about the original creative idea of the Sony ad but it is typical British humour to do a 'spoof' take on something like that. Something along the lines of imitation being the sincerest form of flattery!

You're always welcome to karp on my blog :-) Next post will be of somewhere near where I live like you requested :-)

All this chemistry is making my head spin!
colleen said…
I do believe this will be figured out to the benefit of cancer treatment. I heard on the nightly news about a month ago that breast cancer is down and they're thinking it's related to the fact that less women are using hormone replacement therapy. What would michele say?
It is all beyond me, Dave....I honestly didn't understand most of what you were writing left brain just didn't develop in the same way as my right brain..(LOL)
I'm glad YOU know what you are talking about though....Thanks for the visit, my dear!
Anonymous said…
That's very interesting... Believe it or not, I kind of get it. It helps that I have a pseudo-scientific background. It looks promising at least,

Michele sends her regards,

Carmi said…
You have an innate ability to make the impossibly complex seem understandable by mere mortals. It's a gift, my friend.
Anonymous said…
I'm fascinated that you work in cancer research. I wonder how you feel about cynics like me, who believe that cancer has become such a huge business that a cure would never be "allowed". Maybe small progress here and there, but if it were virtually wiped out like polio, I think our economy would collapse. And maybe the rest of the world's as well?

Spreading cheer from michele's place. ;)

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