Sciencemadness Discussion Board

Interesting cancer drugs?

Blind Angel - 30-1-2007 at 19:55

I'm not sure where this is going, so move it if not appropriate.
I just red this news, the article seem at first very encouraging, so much that they had to place a disclaimer to moderate it a bit. I'm no pro on cancer thingy, I do know that they're members here who do know a lot more on the subject than me and I would like to have their opinion on the subject: Is dichloroacetic acid really that marvellous or is it only another false promise that media are starting to watch?
Here is the article: http://media.www.studentprintz.com/media/storage/paper974/ne...

The_Davster - 30-1-2007 at 21:46

Yeah I've been hearing about that as well. Don't think it was in the 'real' papers, just the student ones. Really interesting considering my local newspaper had a 2 page article on a fabricated stress disease caused by the christmas season. But no blurb even about a potential cure for cancer. And it was in the student papers 2 or 3 weeks ago. (yes, I enjoy reading student papers more than the 'real' ones)

Suppose if 'they' wanted to, the mainstream media could be 'persuaded' to not mention it. After all, something like 60% of the newspapers in Canada are owned by this one guy.

Another article:http://www.expressnews.ualberta.ca/article.cfm?id=8153

Twospoons - 30-1-2007 at 22:51

I saw it on the New Scientist website. The sad thing is no-one wants to pay for trials, as the stuff is not patentable.
Same thing at the local medical school - no funding for research that wont result in a patentable drug!

Maya - 31-1-2007 at 09:05

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi...

Looks like the whole school worked on it

Impressive if it repeats, but cancer is not one disease it is a multitude of diseases

I work everyday doing all the stuff that they just did and I'll wait to see what peer review thinks validation should be done.

Anyways, did anyone notice how long it took them to publish? The reviewers sure asked for a ton of experiments B4 giving them the green light. Cancer Cell is a stickler.

Anyways, this drug is already made by the tonnes by every chemical company in the world and their grandma. Its not like they aren't already making it. You could make it yourself easily. THe real trick is that DCA is not the chemical you would give for a lot of reasons that I won't get into. What you would do is find the actual mechanism by which it works and then find a drug that targets that mechanism in a safe and efficacious manner.



[Edited on 31-1-2007 by Maya]

[Edited on 31-1-2007 by Maya]

chemoleo - 31-1-2007 at 17:46

Ah, I'll see that I can get the full article.
What strikes me is that DCA is likely a nice cytotoxic compound. Why then is it supposedly harmless to normal cells?

Ozone - 31-1-2007 at 18:19

I'd like to read it if you can bet it! I tried, but all I can get though our library is Cancer Cell International. Bummer. I do note, however, that I am always wary of papers with that many contributing authors!

The main problem that I see is the generic systemic application of a cytotoxic entity. Where DCA itself might not be patentable, a cell (say glycolipid) specific vehicle could be.

So, eh, all we need is a molecule (or modified liposome) that homes in on cancer cells and can somehow dump the payload inside.

No mean feat,

O3

Twospoons - 31-1-2007 at 20:58

So its toxic. So what? The cancer is likely to be terminal anyway so what have you got to lose? Have you seen what modern chemotherapy does to people?

The real point is that here is a potential anti-cancer treatment that could be both effective *and* cheap!

longimanus - 1-2-2007 at 11:01

Quote:
Impressive if it repeats, but cancer is not one disease it is a multitude of diseases
I really don't think that that mitochondria-reactivation thing would help a lot - even if the cell is again able to execute apoptosis. What about all that mismatch-repair system defects? OK, it is said that DCA worked with breast cancer cells but I haven't seen any numbers yet.
Quote:
So its toxic. So what? The cancer is likely to be terminal anyway so what have you got to lose?
Hm, I should respectfully disagree. Many patients with cancer are treated successfully, even with minimum chemotherapy, many of them live treir normal lives again. Saying in public that cancer is likely to bring to death is not advisable (that was one of the mistakes of the Minister of Health in my country - nice surgeon - but rather ugly statement).

unionised - 1-2-2007 at 12:11

"I really don't think that that mitochondria-reactivation thing would help a lot - even if the cell is again able to execute apoptosis. What about all that mismatch-repair system defects? "
I may be mistaken but once you restart apoptosis, doesn't that mean the cell dies and the bits get tidied away? After that, who cares about defects?

Unfortunately, if what I just read in New Scientist is correct this stuff is a promising lead rather than a drug in its own right. "(DCA) is genotoxic, hepatotoxic and teratogenic in animals, all at doses well below what would seemingly be necessary..."
The article also berates New Scientist for raising false hopes.

Maya - 2-2-2007 at 05:03

Quote:

I really don't think that that mitochondria-reactivation thing would help a lot - even if the cell is again able to execute apoptosis. What about all that mismatch-repair system defects?


There are various DNA mismatch-repair detection pathways but in a normal cell, it will commit to programmed cell death if it is unable to repair the damage. In a Dna repair damage type of disorder like Fanconi Anemia, the damage does not lead to apoptosis but rather to cancer, typically AML or MDS/ Leukemia.

Moreover, each type of cancer is different in the signaling pathway defect which is responsible for that specific cancer. To say that we can inhibit or restart a certain pathway does not address the other mechanisms with abnormal signaling.

And yes, DCA is cytotoxic. They used 5 mM in their studies :o
I don't think thats a good thing. Instead find another compound that targets the same pathway but at a much lower concentration and with less toxicity

longimanus - 3-2-2007 at 02:22

Quote:
I may be mistaken but once you restart apoptosis, doesn't that mean the cell dies and the bits get tidied away? After that, who cares about defects?
The problem is that the MMR defects could be hereditary so that it could affect whole cell line. => massive deffects in DNA, massive apoptosis. It doesn't sound too good to lose a cell line, does it? I'm not saying that this is 100% sure, but... Somehow reminds me of the case with the excessive immune response. Genetic therapy with raw genes sounds a little more promising to me in that case.

chemoleo - 3-2-2007 at 08:34

see attachment for article

Hmm...attachments are not attached (pdf), both in firefox and IE. Can anyone tell me why this might be?

[Edited on 3-2-2007 by chemoleo]

Nicodem - 3-2-2007 at 09:33

Is it even possible to upload 2.6MB in an attachment? Here is the rapidshared paper. (Edit: Damn! I found it is freely accessible at University of Alberta server anyway)
Quote:
Originally posted by Maya
And yes, DCA is cytotoxic. They used 5 mM in their studies :o

To achieve 5mM concentration in organs one would have to take tens of grams of sodium dichloroacetate, depending on the efficiency of the kidneys to remove it form the system, but probably even up to 50g per day! That is still below its LD50 (for intraperitoneal administration to mice it is more than 3000mg/kg) *. The LD50 makes it relatively non toxic acutely, but I bet 50g orally would make you feel terribly seek, not to mention the chronic effects.
Chronic exposure to dichloroacetates does not seem very safe but still way better than cancer:
Quote:
Dichloroacetic acid
Patients diagnosed with genetic disorders, such as familial hypercholesterolaemia
(common disorder of lipid metabolism associated with a high risk of early mortality from
coronary artery disease) or various mitochondrial disorders and, as a result, treated daily with
DCA (sodium salt) for periods greater than 4 months were found to develop peripheral
neuropathy (loss of reflexes and muscle weakness) and in one case hepatomegaly (enlarged
liver) (Moore et al., 1979; Spruijt et al., 2001; Izumi et al., 2003).
Humans exposed in an occupational setting to concentrated mist or vapour of DCA may
develop pulmonary oedema several hours after exposure (CHEMINFO, 2003c).

The same source gives also the oral LD50 for dichloroactic acid salts (it does not mention the cation, but I would assume it is about sodium dichloroacetate):
Rats: 4480 mg/kg
Mice 4845-5500 mg/kg
Clinical observations: Semi narcosis, narcosis.

Edit: The chapter 10.2.2 (pages 27-28) describing the chronic effect of sodium dichloroacetate on rats is worth reading. Note the huge doses used!

[Edited on 3-2-2007 by Nicodem]

chemrox - 9-2-2007 at 22:36

I'm sure you've all heard of 'chemo-brain'. Chemotherapy is taking poisons. I have a lawyer friend who doesn't practice lawq anymore as the result of chemobrain. She did survive lung cancer however. Has her back and the cognition is returning but she has also recovered from law. If DCA could cure my cancer and it looked like nothing else would I would certainly risk the effects. Some research on mitigating the toxicity of DCA seems appropriate. As someone said, there's no money in it (DCA) for the companies. Maybe there are some patents to be had in the mitigation. that or alteration of the compound or a compound to deliver the moiety where it's needed but not everywhere in the body.

Sauron - 10-2-2007 at 01:41

I guess anyone who has looked into oncological therapeutics knows about 5FU (5-fluorouracil.)

Well, there's a related substance that potentiates the effects against tumors while mediating side effects so patients can tolerate the 5FU better.

TAU triacetyluridine.

It's in FDA now not for cancer but for something else, but once approved for one use it's a fast track to other uses.

Already on the grey market being touted for almost anything just like hydrazine sulfate and lots of other things that are being sold to desperate folks. However you can't blame the molecule for the greed and avarice of some and the cupidity of others.

I got this tip from a patent examiner in DC. He wanted to go into business.

longimanus - 10-2-2007 at 10:56

Quote:
...or a compound to deliver the moiety where it's needed but not everywhere in the body.

Or just that liposomes that are under investigation from already lots of years - loaded with the anti-tumor agent and with tumor-cells specific antibodies in the lipid bilayer. Hm, I wonder what happened with this - it is not on the news but I still doubt it's abandoned.