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Thalidomide

arcticpenguin

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http://news.bbc.co.uk/1/hi/health/2709093.stm
Researchers in London have discovered that drugs based on thalidomide can destroy cancer cells by forcing them to commit suicide.
...
The drug was marketed in the 1950s and 1960s as a cure for morning sickness. It was banned after mothers who took it gave birth to deformed children.
...
"We were surprised at the ability of this class of drug to kill cancer cells but leave normal cells apparently unaffected."
 
I read awhile ago about how Thalidomide also works great with I think it was Leprosy. The government is scared to have the drug available because of it falling into the wrong hands, or a doctor prescribing it to a pregnant woman etc.

I think it's great to find a good use for this drug, as long as it isn't used for morning sickness!

Question: What do they mean by the cancer cell committing suicide? Do they mean that it doesn't split?
 
Denise said:

Question: What do they mean by the cancer cell committing suicide? Do they mean that it doesn't split?
Click to expand...
Try looking up "apoptosis" - programmed cell death.
 
Denise said:
I read awhile ago about how Thalidomide also works great with I think it was Leprosy. The government is scared to have the drug available because of it falling into the wrong hands, or a doctor prescribing it to a pregnant woman etc.
Click to expand...

There are many drugs that shouldn't be given to pregnant women. What reason (aside from the political oines) could there possibly be for not allowing it?

(That's not directed at you, D; just a general question.)
 
I'm a clinical cancer research coordinator in Washington, DC. Where I work, we are currently conducting a prostate cancer trail using single agent thalidomide. Also, a new thalidomide derivative is in phase II clinical trials with multiple myeloma as its indication.

The issue of thalidomide causing horrid birth defects has little to do with its approval with cancer for indication of use. Most chemotherapies are not exactly friendly to fetuses. Thalidomide simply hasn't been through all the proper clinical trials in order to be approved for a specific type of cancer. Give it a little time. If the FDA will approve accutane for acne, surely they will approve thalidomide for cancer if it proves to hold any efficacy.
 
While I don't want sound like a conspiracy nut, I think that the handling of Thalidomide was meant as a warning for drug companies.

If I recall correctly, it was originally used to treat pregnant women for morning sickness, but was never tested in pregnant animals. After human babies were born with rather substantial deformities, animal testing was conducted. These tests revealed the same outcomes in animal pregnancy. The drug was subsequently banned.

If more recent tests are finding other benfits, then the drug should be thoroughly tested and approved for those new applications, and health professionals educated as to the negative side effects. This is what is done with other drugs, and if it is not done with Thalidomide, then must wonder if there are not other motivations.

Incidentally, Thalidomide actually exists as two enantiomers. One gave relief of morning sickness, while the other caused deformities. One could speculate that the latter enantiomer interferes with the cell cycle, thus conferring the beneficial effects in cancer patients. This would be somewhat ironic if it indeed proves to be the case.

More info on Thalidomide:

Background ---- http://www.atdn.org/simple/thalid.html

Chemistry ---- http://www.rlc.dcccd.edu/MATHSCI/reynolds/thalidomide/chemistry/chemistry.htm

Mr. Turquoise

Edited to add: Lucid One posted as I was typing, and made the point more clearly. Oh well.
 
(I am not sure how relevant this point is since the article is talking about thalidamide based drugs, and the same enantiospecific effects may not be applicable to the derivatives....)

But it is interesting to know that, both enantomiers have both theraputic and tetragenic effects. The interesting thing is it racemizes in vivo (i.e. even if you take one "pure form" while bouncing around your body, some of the drug gets converted to the other)...I don't know if it has been shown as to which of the less obvious physiological effects are due to which enantiomer....
 
If I recall correctly, the anti-leprosy and anti-cancer activity is in one handedness of the drug, and the teratogenesis is the other handedness.

But they are hard to separate, I gather.
 
Researchers in London have discovered that drugs based on thalidomide can destroy cancer cells by forcing them to commit suicide

I am curious. I first heard about this 11 years ago when my late wife was being treated for cancer. Why is it news now? Has there been new development?
 
Mark,

I'm sorry to hear about your wife. Was she treated in a country other than the United States by any chance? I am not sure how long thalidomide has been used in other countries to combat cancer; however, it certainly isn't an available treatment option in the U.S. outside of the few clinical trials that have popped up in the past 3 or 4 years.

Celgene, the manufacturers of Thalomid (thalidomide), only have FDA approval for thalidomide to be used against leprosy. See the drug package insert for Thalomid under the "Indications and Usage" section.

http://www.celgene.com/images/pdf/$FILE/Thalomid_Pl.pdf

Being involved in cancer research, I have come to realize that the media reports advances in cancer research when it is convenient to them. They also like to make every advancement seem like the next cure for cancer. I don't think that the article that started this thread is breaking news. All that really happened is that some researches found evidence that the mechanism through which thalidomide fights cancer is the induction of apoptosis.
 
Thanks, Lucid One (Cool name, btw),

She was treated in the U.S. I didn't mean to imply she was treated with thalidomide...it was just one of the ideas bandied about at one point. She was to be one of the first 8 people in the U.S. to receive an experimental (and at the time very promising; 100% effective in mice) gene therapy. Sadly, she never got the chance, and the therapy turned out in human tests to be only mildly effective, and then only for a short time (a few weeks if memory serves).

With the myriad forms of cancer, and the variations in each type introduced by eash person's own genetic make up, I am no longer optimistic that they will ever find a really effective, magic bullet type, cure. Therapies will no doubt continue to improve, and lengthen lives, but when metastatic cancer reaches the explosive stage, there is nothing on earth that will stop it; I don't think there ever will be; I hope I am wrong.
 
Mark said:
With the myriad forms of cancer, and the variations in each type introduced by eash person's own genetic make up, I am no longer optimistic that they will ever find a really effective, magic bullet type, cure.
Click to expand...

I would have to say that I agree with you. Finding an all-encompassing cure for cancer is analogous to finding a cure for all viruses or all bacterial infections.
 
Mr. Turquoise said:


If I recall correctly, it was originally used to treat pregnant women for morning sickness, but was never tested in pregnant animals. After human babies were born with rather substantial deformities, animal testing was conducted. These tests revealed the same outcomes in animal pregnancy. The drug was subsequently banned.
Click to expand...

I will have to rebut this being a pharmacology/toxicology student.
It was actually tested on pregnant animals. To the rigorous 1950's standards on not one, but two species of animal. Unfortunately, the mice and rats were not sensitive to the teratogenic effects, so the drug companies investigated other animals and found ruminants sensitive to mutagenic and teratogenic drugs and are now used by law in the U.K. for screening and other toxicological testing.

(It was also found the d-enantiomer was the teratogenic component, due to increase in retinoic acid formation for all you bio/medical folks out there)

The big conspiracy was on the anti-vivisectionist forums, this was probably due to the amount of animals increasing in testing after the Thalidomide tragedy.

A good (propaganda) article, on the side of animal studies can be found here.


Another rather more technical, but under used resource is Entrez-PubMed .


Good luck!
 
Hi all.

This is actually a thread on which I can contribute (I'm amazed). I was involved in research on the efficacy of thalidomide as a single agent in renal cell carcinoma (kidney cancer). We were looking at thalidomide's reported potential as an anti-angiogenic agent - a drug able to interfere with the tumour-mediated development of new blood vessels. This property of thalidomide has been suggested as the mechanism underlying the range of birth defects that are seen in exposed offspring. It's also why thalidomide has become a treatment option for leprosy and other disorders where inappropriate blood vessel development is thought to take place.

Unfortunately, we found thalidomide was, at best, not effective and at worst, actively promoting more aggressive tumour growth. We proposed a mechanism for this based on PCR data.

Clinical studies since then have basically found the same thing in renal cell carcinoma. I understand though it is showing some promise for treatment of other types of cancer, like multiple myeloma. It's possible that if used in combination with other drugs it might still be useful in kidney cancer too, but so far, no joy.

Nice to meet you all.

:)
 
sadluxation said:


I will have to rebut this being a pharmacology/toxicology student.
It was actually tested on pregnant animals. To the rigorous 1950's standards on not one, but two species of animal. Unfortunately, the mice and rats were not sensitive to the teratogenic effects, so the drug companies investigated other animals and found ruminants sensitive to mutagenic and teratogenic drugs and are now used by law in the U.K. for screening and other toxicological testing.
Click to expand...

Thank you for filling a few details sadluxation. I was a bit rusty on the story. Anyway, I read that researchers weren't specifically looking for teratogenic effects, which is why they didn't report any, and I interpreted this to mean that they didn't study the drug's effects in pregnant animals. That was a careless assumption on my part.

I also didn't mean to suggest that I buy into the conspiracy elements of the story, but the tradegy that unfolded does highlight the importance of conducting thorough trials before a drug is used in humans (particularly pregnant humans), which is why it is so frequently cited by both sides of the vivisection debate.

BTW, you said that two species were required for study in the 50's. How many is it now?

Mr. Turquoise
 
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