Mike the Mad Biologist

There’s an article in the New Scientist about researchers who are using dichloroacetate (‘DCA’) to treat many different cancers. According to the article, here’s what DCA does:

Evangelos Michelakis of the University of Alberta in Edmonton, Canada, and his colleagues tested DCA on human cells cultured outside the body and found that it killed lung, breast and brain cancer cells, but not healthy cells. Tumours in rats deliberately infected with human cancer also shrank drastically when they were fed DCA-laced water for several weeks.

DCA attacks a unique feature of cancer cells: the fact that they make their energy throughout the main body of the cell, rather than in distinct organelles called mitochondria. This process, called glycolysis, is inefficient and uses up vast amounts of sugar.

Until now it had been assumed that cancer cells used glycolysis because their mitochondria were irreparably damaged. However, Michelakis’s experiments prove this is not the case, because DCA reawakened the mitochondria in cancer cells. The cells then withered and died.

I looked at the paper in Cancer Cell and the conclusions seem plausible, but I would be interested in what the professionals think of it. What does tumor reduction mean in a clinical sense? Is that actually significant, or do many compounds reduce human tumors implanted into rats? Finally, would it be possible for cells to develop resistance to DCA? I wouldn’t think so, since it seems to be a pretty small compound that could diffuse into the cell (although maybe a mitochondrial mutation could prevent the mitochondria from ‘reawakening.’)

Just curious.

My apologies if this has already been discussed. As the members of ScienceBlogs (and probably most of our regular readers) know, the search function is fubar.

Comments

#1 kalev
January 18, 2007

you are interested in what the professionals think…how condesending you are…are Canadaian Scientists somehow a sub class of humans or should I say American scientists
#2 Joshua
January 18, 2007

It’s customary, after all, in the business of medicine to seek second opinions.

The wider point is that science relies on consensus. No one study, no matter how good, can or should ever be the final word on a topic.
#3 Andrew Wade
January 18, 2007

This process, called glycolysis, is inefficient and uses up vast amounts of sugar.

Not in the middle of a poorly vascularized lump it won’t… Presumably these cells will have a very low metabolism.
#4 The Cheerful Oncologist
January 18, 2007

kalev: There’s a “c” in condescending, but I’m sure you know that.

Joshua: I agree – DCA may work in vitro but not in vivo. Looks like a fascinating line of research, though.

Andrew: is this lump benign or malignant? Malignant tumors are highly vascularized and have high metabolism, thus they light up when injected with 18-FDG (for a PET/CT).

Mike: I was going to blog on this paper but am glad you decided to. What do you think about this “re-awaken the mighty mitochondria” hypothesis?
#5 Orac
January 18, 2007

I was thinking of blogging on this paper, too. Heck, I even downloaded it. But Your Friday Dose of Woo will not wait; so I didn’t have time tonight to deal with it. I may post a brief something tomorrow if I have time and then blog the paper itself next week.

As for kalev, he seems to have a bug up his butt about something; it was quite clear that Mike was not denigrating Canadian scientists.
#6 Andrew Dodds
January 19, 2007

I actually cancelled my subscription to the New Scientist because they were getting so far away from the ‘Scientist’ bit towards that ‘Tabloid Journalist on a slow news day’ bit…

This review paper seems interesting background reading.. may take a while though!
#7 Andrew Wade
January 19, 2007

Andrew: is this lump benign or malignant?

Benign. They seem to have left out a few steps on the road to cancer. The “poorly vascularized” I’m getting from their description of the cells in the middle of the lump not getting enough oxygen. I’m no biologist (which I should have mentioned); I don’t know for sure that such cells would have trouble getting much glucose when their own supplies run out, but it seems like a straightforward enough inference.
#8 Mike the Mad Biologist
January 19, 2007

kalev,

I was referring to me. I’m not an oncologist.
#9 Mike the Mad Biologist
January 19, 2007

TCO,

the Mitochondrial Awakening does seem plausible (although I’m not an expert). The real issue is does it actually work.
#10 Robster
January 21, 2007

Not an oncologist, but my PhD did focus on cancer research.

What does tumor reduction mean in a clinical sense?

Decreased tumor burden is almost always a good thing for the patient. It doesn’t mean that a treatment will be a long term success, but it does mean that any net growth is negative.

Is that actually significant, or do many compounds reduce human tumors implanted into rats?

Lots of compounds do cause tumor reduction in rodent models, but don’t work that well in humans. It is promising, though. Camptothecin works great in rodents, but fails in humans. Analogs work much better, but still not as well as the rodent experiments suggested that they would. Albumin binding differences between rodent and human are thought to be the primary issue with that drug.

Finally, would it be possible for cells to develop resistance to DCA?

Absolutely. Whether it be via an exclusionary transport system or a metabolic pathway, resistance is always a risk. It does have a known side effect profile, which is useful. Hopefully, the therapeutic dose will be something that the patient can tolerate.
#11 Bucc
January 23, 2007

Robster, how about trials on dogs : do the results resemble those obtained from mice or from humans ? My dog has pancreatic cancer with metastasis infiltrating other organs, and because she has only one kidney, DCA appears to be our only shot at trying to slow down tumor growth and proliferation. Can we expect similar results as the study shows ?

TIA
#12 Robster
January 26, 2007

Bucc, I don’t know. Cancer is a lump name for a hundred different diseases, some differing from species to species. Without knowing what a safe and effective dose and dose pattern, I can’t give you any suggestions. Best of luck to you.