Disulfiram: New study below [1a] with... - Advanced Prostate...

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Disulfiram

pjoshea13 profile image
31 Replies

New study below [1a] with story [1b]. (Read the story - not the paper.)

Disulfiram is an old alcohol aversion drug. It would be terrible if it turned out to be effective against PCa. LOL

...

"First, they carried out a nationwide epidemiological study of more than 3,000 Danish people, which showed that cancer patients who continued to take disulfiram were much less likely to die from cancer compared with those who stopped taking the treatment.

"Patients with breast cancer, colorectal cancer, and prostate cancer all benefited from disulfiram's effects.

"Then, the researchers carried out in vitro studies of cancer cells and in vivo studies of mice and identified the metabolite of disulfiram that enables the drug to fight off cancer: the so-called ditiocarb-copper complex.

"The researchers also identified ways to further detect and analyze how this metabolite complex accumulates in tumors.

"Finally, and importantly, the researchers found the molecular pathway through which this ditiocarb-copper complex acts to suppress cancer cells."

...

There have been a number of Disulfiram papers over the past decade. Here's one from last year [2]:

"Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution"

"Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer."

-Patrick

[1a] nature.com/articles/nature2...

[1b] medicalnewstoday.com/articl...

Previous studies have demonstrated that the alcohol abuse drug disulfiram has anticancer properties. But until now, researchers had not found the mechanism by which the drug can target cancer. New research sheds light, paving the way for the repurposing of the drug.

A new study — published in the journal Nature — uncovers the mechanism and the molecular pathway through which the popular alcohol-aversion drug disulfiram can fight off cancer.

This study was conducted by an international team of researchers led by Jiri Bartek, of the Danish Cancer Society Research Center in Copenhagen.

Disulfiram — also known by the brand name Antabuse — has been used for decades to treat chronic alcohol abuse. While the drug is not a cure for chronic alcoholism, it does discourage those with alcohol abuse issues from drinking.

Previous studies have shown that the drug has anti-tumor activity both in vitro and in vivo. But as Bartek and colleagues explain in their paper, the drug hasn't yet been repurposed for cancer treatment because the mechanism and molecular pathways through which the drug may act against cancer were unknown.

As the study's authors explain, given the rising global incidence of cancer and the failure of many medications in the face of tumor resistance, identifying new possibilities for using already existing drugs is key.

In fact, the World Health Organization (WHO) estimate that in the next two decades, the number of new cancer cases will rise by 70 percent. Cancer is already the second leading cause of death worldwide.

In this context, drug repurposing is a safe, cost- and time-effective alternative. Testing new drugs can be expensive and time-consuming, but drug repurposing uses medications for which most of the relevant testing has already been done.

So, Bartek and colleagues set out to unravel the mystery of disulfiram's anticancer properties.

First, they carried out a nationwide epidemiological study of more than 3,000 Danish people, which showed that cancer patients who continued to take disulfiram were much less likely to die from cancer compared with those who stopped taking the treatment.

Patients with breast cancer, colorectal cancer, and prostate cancer all benefited from disulfiram's effects.

Then, the researchers carried out in vitro studies of cancer cells and in vivo studies of mice and identified the metabolite of disulfiram that enables the drug to fight off cancer: the so-called ditiocarb-copper complex.

The researchers also identified ways to further detect and analyze how this metabolite complex accumulates in tumors.

Finally, and importantly, the researchers found the molecular pathway through which this ditiocarb-copper complex acts to suppress cancer cells.

They write, "[O]ur functional and biophysical analyses reveal the molecular target of disulfiram's tumor-suppressing effects as NPL4, an adaptor of p97 [...] segregase, which is essential for the turnover of proteins involved in multiple regulatory and stress-response pathways in cells."

"Our results help to explain the anticancer activity of the alcohol-abuse drug disulfiram," say Bartek and his colleagues.

"From a broader perspective, our study illustrates the potential of multifaceted approaches to drug repurposing," they add, "providing novel mechanistic insights, identification of new cancer-relevant targets, and encouragement for further clinical trials."

The researchers conclude:

"[Disulfiram is] an old, safe, and public domain drug that might help to save lives of patients with cancer worldwide."

[2] ncbi.nlm.nih.gov/pmc/articl...

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31 Replies
joeoconnell profile image
joeoconnell

when i quit drinking alcohol 43 years ago i was on Antabuse

pjoshea13 profile image
pjoshea13 in reply to joeoconnell

Joe,

That's the stuff. How did it feel towards the end? Easily tolerated?

-Patrick

joeoconnell profile image
joeoconnell in reply to pjoshea13

i developed an allergic reaction to it , and they took me off it. may have had to do with i was using Vitalis hair tonic on my head and it contains alcohol, didn't realize it at the time

in reply to joeoconnell

Vitalis and brylcream. Those were the days.

Neal-Snyder profile image
Neal-Snyder in reply to

A little dab'll do you.

herb1 profile image
herb1

the kiss of death: "public domain drug". It will never get the trials needed; but of course some will go ahead and use it anyway. herb

Billash profile image
Billash in reply to herb1

Sad but true Herb, it does sound good to me as I do not drink at all any more. Plus It is inexpensive. I have no drug coverage.

pjoshea13 profile image
pjoshea13 in reply to Billash

And yet, Metformin is a dirt-cheap old drug that has gained traction. clinicaltrials.gov just returned 30 studies for <prostate metformin>.

Even for <prostate Disulfiram> there are two studies:

1] Johns Hopkins University

"A Multi-institutional Translational Clinical Trial of Disulfiram in Men With Recurrent Prostate Cancer as Evident by a Rising PSA"

clinicaltrials.gov/ct2/show...

2] Duke University Medical Center

"A Phase Ib Study of Intravenous Copper Loading With Oral Disulfiram in Metastatic, Castration Resistant Prostate Cancer"

clinicaltrials.gov/ct2/show...

-Patrick

BigRich profile image
BigRich in reply to pjoshea13

Patrick,

What are the side effects to the drug, if you don't drink alcohol?

Rich

I have hypertension, kidney disease, and diabetes.

Rich

pjoshea13 profile image
pjoshea13 in reply to BigRich

Rich:

rxlist.com/antabuse-side-ef...

-Patrick

BigRich profile image
BigRich in reply to pjoshea13

Patrick,

Thank you.

Rich

in reply to pjoshea13

I saw my general practitioner a couple of days ago and spoke about metformin being useful for someone with prostate cancer. He wasn't receptive at all. Maybe the wrong doctor to be talking to.

Dan59 profile image
Dan59 in reply to

It is best to print out these studies on whatever, ie metformin and bring them into your medical Oncologist to review. Perhaps if you had a peer reviewed paper in hand your GP would have been more receptive.

Neal-Snyder profile image
Neal-Snyder in reply to

It all depends. I knew the medical oncologists at my hospital won't prescribe anything unless there's a completed Phase 3 trial showing the benefit for PCa patients. I also knew my PCP is a very sympathetic guy. I gave him the references Patrick provided for 1000 mg, & he prescribed it. Later I gave him Patrick's reference for 2000 mg, & he increased the dosage.

Billash profile image
Billash

I have been met free until last week, scan showed 2 ribs lit up like a christmas tree, new biopsy next week. With my Gleason 9 I will try most any affordable treatment.

Kuanyin profile image
Kuanyin

Thank you for the post. Your comparison of Disulfuram with Metformin is very perceptive. Although there was no financial incentive for drug companies to study Disulfuram vis.a.vis PCa, nevertheless, many researchers have chosen to study the connection between PCa and Metformin, if for nothing else than for professional gain. That said, I checked the Johns Hopkins study which was completed over five years ago. It was a two-year study that involved two dosages: 250 or 500 mg taken once a day. The researchers have had plenty of time to evaluate the effectiveness of Disulfuram on PCa, yet, as far as I can see, they have published no results. Even if the drug were not effective at either dose level, one would think that they could have at least told us. My computer has been down and I have had to use my wife's which is not convenient, so I have not had the opportunity to read about the side effects of the Disulfuram, but several members of the forum are familiar with it and appear to have taken it. Would it be worthwhile to contact Johns Hopkins to enquire about the findings of the study?

Neal-Snyder profile image
Neal-Snyder

Would that avoid the negative effect of Anitbuse if you choose to have an occasional drink? It seems like a shame to have to forego that if you aren't a problem drinker.

E2-Guy profile image
E2-Guy

What the hell...I think I'm going to try the 'disulfiram' for a month or two! A one month's supply of 250 mg tablets (80 mg 3 x daily) is $3.75 here in Thailand. I don't drink alcohol.

MabrachonJP profile image
MabrachonJP in reply to E2-Guy

I also live in Thailand and just had my biopsy. I had a MRI first which showed a 14mm cyst on my prostate but not in my bones yet. My PSA is 33 and my doctor said 99% PC but they would not treat me at the cancer center without a biopsy.. now waiting on my results but in the meantime I want to start taking disulfiram. Ronronhu have you started taking it yet? Any side affects? R u also taking a copper supplement?

E2-Guy profile image
E2-Guy in reply to MabrachonJP

Hi MabrachonJP,

At this time I haven't started taking anything...I am waiting until my next PSA which I will get in two to three weeks. My last PSA was 0.67 which of course is over three times the level (0.2) at which recurrence is obvious after a man has had an RP. As I have previously mentioned, I have had no adjuvant therapy (other than the recent sacral lymph node resection surgery), no form of ADT yet. I will most likely have to start on something (disulfiram, Avodart, or oestrogel) in the very near future in hopes that one of them may slow the progression. I'm going to try only one for a couple of months to see if it has any effect, if not, I will try another while closely monitoring my PSA. I will keep you apprised of my progress or lack of. Where in Thailand do you live? Hoping that your biopsy is negative. Best regards, Ron

MabrachonJP profile image
MabrachonJP in reply to E2-Guy

How old are you? I believe you are not correct in your accessment.. "Cancer Research UK uses the following rough guide: 3 ng/ml or lower is considered in the normal range for a man under 60 years old. 4 ng/ml or lower is normal for a man between 60 to 69 years old. 5 ng/ml or lower is normal for a man 70 years old and over."

E2-Guy profile image
E2-Guy in reply to MabrachonJP

Hi Mabrachon,

Thank you for your reply; however, the parameters that you have listed are for a man who hasn't had an RP. After a man has his prostate removed his PSA should be undetectable. At 0.2 we know that the cancer is recurring either locally or distant. I am 74. Ron

MabrachonJP profile image
MabrachonJP in reply to E2-Guy

Ok Ron, ic. I ordered disulfiram from an online pharmacy today as I could not find it at any of the major pharmacies in Pattaya. Some indicated it has not been in stock for over a month. I ordered 60 500mg for about 74 USD including expedited shipping. I plan on taking half a tablet a day. I eat plenty of mushrooms and drinking Chaga mushroom tea three times a day which I think will give me plenty of copper which as you may know helps the disulfiram be more effective. I get the results of my biopsy tomorrow and I expect the worse.. but I have been preparing for the battle for awhile now.. I have been recommended for radiotherapy already but they would not treat me at the cancer center without a biopsy... I will see if brachytherapy is an option for me. I have already started some alternative medicine protocols which will now include the disulfiram and I hope to start the conventional medicine treatment in the next few days. Where in Thailand do you live?

E2-Guy profile image
E2-Guy in reply to MabrachonJP

Mabrachon, Can you cancel your order? 60 - 500mg tablets are $14 USD here in Naklua. You can call me at: 091-134-9955

kanzan profile image
kanzan in reply to E2-Guy

I've purchased Disulfiram / Dizon from alldaychemist for less than .20 cents/pill. My experience is it may have raised my blood pressure some, but I am also taking other medications as well....Since is seems to work best with copper to kill PC, and I really don't want to take more copper--possible alzheimers risk, I've decided to just take one tablet on the weekend. For the other poster, no alcohol with this med which has a fairly long half life (60-120 hrs).

snoraste profile image
snoraste

Do we know anyone in the community that has successfully incorporated “copper” into their daily regiment?

pjoshea13 profile image
pjoshea13 in reply to snoraste

In my case, I do what I can to avoid copper. There are copper stains in our sinks that are a pain to remove. We have copper pipes, but the pH of our water is high & I would not have expected copper from the pipes to be the source.

There have been PCa studies aimed at depleting copper, which is required for angiogenesis. When tumors outgrow their blood supply, copper is essential for the formation of new blood vessels.

Of course, if copper is needed for a therapy to be successful, that's another matter. Copper is included in some multiminerals. I don't know why, since deficiency is unusual. & I see that there are plenty of stand-alone supplements, e.g.:

swansonvitamins.com/swanson...

-Patrick

GeorgesCalvez profile image
GeorgesCalvez

I think that disulfiram and copper II are ineffective on their own, however in aqueous solution they form a disulfiram copper II complex that is effective against cancer cells.

pubs.rsc.org/en/content/art...

pjoshea13 profile image
pjoshea13 in reply to GeorgesCalvez

Thanks George! Interesting read. -Patrick

Copper is good to avoid. But what would you do if your blood levels would be 8.4 mcmol/l (normal range 12-24), being zinc at 13.4 mcmol/l (8-20 normal).

1) do nothing

2) diminish zinc citrate intake (actually 50mg)

3) supplement copper (ev. naturally)?

pjoshea13 profile image
pjoshea13 in reply to

I suspect that it's difficult to diagnose a copper deficiency. The symptoms are so non-specific.

I'd be inclined to include foods high in copper. Shellfish. Dark chocolate. Beef liver is highest: 458% RDI from 1 oz!

-Patrick

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