214 replies to this topic

[mag1]

Something else should be mentioned.

When the doctors began treatment with 3-BP, they immediately pushed a bolus dose over a few minutes intra-arterially.
The first day's dose was a total of 250 mg.

The obvious question is: How did they know such a dose was safe?

At the wrong dose 3-BP would quickly kill a patient.
They seemed pretty confident that this would be safe.
If I had been the doctor involved in the care of the patient, I would not have done
a rapid bolus push of 3-BP without knowing whether or not it was safe.

The suspicion is that other patients had already been quietly treated with 3-BP.
This would not be entirely unexpected. There are large numbers of available end stage cancer patients. Under German law, doctors are allowed to use their professional judgement in choosing treatments.

If this were in fact correct, then patients with severe illness might have been treated and the toxicity (or lack thereof) of 3-BP treatment would already have been known before treatment began with the German patient.

[mag1]

The melanoma report adds a different perspective on 3-BP treatment.

http://www.ncbi.nlm....les/PMC4110469/

The article presents evidence that this patient did not experience toxicity due to 3-BP treatment.
The article notes that on the basis of serum ALT, AST, total bilirubin, albumin, etc. renal and liver
function was determined to be normal.

There are a few interesting aspects of this patient report that should be noted.

The patient was treated with IV 3-BP.
This is important as it indicates that 3-BP might be used safely to treat widespread illness.

Eight IV treatments of 3-BP (between 1 and 2.2 mg per kg) did not result in detectable toxicity.
However, there was also no great therapeutic effect either.
When paracetamol was combined with 3-BP, a massive anti-tumor effect was seen immediately.

Paracetamol might allow for a minimal exposure to 3-BP.
Combination treatment could allow for extreme responses without heavy repeated doses of 3-BP.

[pone11]

I am becoming somewhat confused by the argument.

The noted quote from the patent used dosages of 20mM and 50mM etc. intravenously.

The German patient received intra-arterial treatment.
The description in the patent did not find toxicity in animals when they were treated with 3-BP using the optimal intra-arterial liver protocol.

"Rabbits treated with 25mL of 1.75 mM 3-bromopyruvate had 100% tumor cell destruction without any damage to the normal liver"

The medical experts in the German report used a wide range of biomarkers to assess liver toxicity. Liver toxicity was not found. In light of the evidence presented in the article, I do not understand why the possibility of liver toxicity continues to be suggested.

In fact, the article notes "Regeneration of liver tissue was also observed and the data are being analyzed for future publication." The authors claim they have direct evidence that the liver was recovering and perhaps they could also show that 3-BP treatment did not cause toxicity. Liver biopsy likely was performed during 3-BP treatment (as might be expected).

 

I'm also confused.  You selectively quote just the things that make your initial point that there is no toxicity, and you selectively do not quote from your own sources - and ignore posts of others - showing that there is probably destruction of adjacent "normal" cells at some dose.

 

I don't think we are going to resolve this.  It appears to just be your style to keep repeating the same studies and ignore the points other people make.

[mag1]

The toxicity concerns raised on this thread have been the focus of ongoing 3-BP research. Over the last 15 years improvements have been developed. The microencapsulation of 3-BP and the combination with paracetamol were ways of minimizing 3-BP exposure while maximizing therapeutic results.

The results with paracetamol in the melanoma patient were especially noteworthy. Using 2.2 mg/kg injected IV, along with paracetamol, the metastatic melanoma patient had a massive anti-tumor response. This is somewhat surprising as this was an intravenous dose. It spread through the patient's body and yet was still effective. Very impressive. The German report used a dosing of 2-3.5 mg/kg for TACE delivery. This would appear to be a very large dose, delivered to a small volume in comparison to the metastatic melanoma patient.

Perhaps the dosing in the liver cancer patient could have been substantially lower with combination treatment of paracetamol. This would have greatly helped in reducing concerns of 3-BP toxicity. Smaller and fewer doses of 3-BP could then have been used.

[mag1]

Wow, synergistic combination effect of rapamycin and 3-BP. Synergistic as in multiplicative benefit.

Anyone have the numbers? How much of a multiplicative effect?

 

No liver toxicity found in mouse models of lung cancer prevention using aerosol delivery of both drugs.

 

 

Cancer Prev Res (Phila). 2015 Feb 2. pii: canprevres.0142.2014. [Epub ahead of print]

Enhanced Antitumor activity of 3-bromopyruvate in combination with rapamycin in vivo and in vitro.

 

http://cancerprevent...PR-14-0142.long

 

 

 

 

 

 

[pone11]

 

Wow, synergistic combination effect of rapamycin and 3-BP. Synergistic as in multiplicative benefit.

Anyone have the numbers? How much of a multiplicative effect?

 

No liver toxicity found in mouse models of lung cancer prevention using aerosol delivery of both drugs.

 

 

Cancer Prev Res (Phila). 2015 Feb 2. pii: canprevres.0142.2014. [Epub ahead of print]

Enhanced Antitumor activity of 3-bromopyruvate in combination with rapamycin in vivo and in vitro.

 

http://cancerprevent...PR-14-0142.long

 

 

The abstract of your link is behind a paywall.  Are you working in a healthcare environment that gives you access to that?

 

Here is the abstract of the study he was trying to post:

http://cancerprevent...R-14-0142.short

[mag1]

I was not sure which url for the article to post.

 

The submission date on the article is a sobering reminder of how dated scientific research can be (even when it is hot off the press).

The posted article was submitted April 2014!

Scientific articles are carefully scrutinized before being sent for publication. How is such a delay justified?

 

Why doesn't the scientific publishing community publish "roughs" or "betas"? That is what is done with software.

The modifications made after the authors have sent it for publication likely would not be substantive.

The ethical implications of withholding medically relevant information from patients for such an extended period of time deserve careful contemplation.

It is not entirely clear whether the current publication practice complies with international law.   

 

 

The quality of the scientific literature might even be enhanced if websites (perhaps even this one) or other reviewers provided commentaries 

on the "roughs". Authors could then integrate such ideas into the final version of their article. Reviewers of such articles would be interested to know

which suggestions and critiques were deemed worthy of rebuttal by the authors.     

 

This form of democratic peer review could greatly enhance the quality of research. Peer review probably often involves the input from a small group of like thinking individuals. Important questions and clarifications might never occur to such groups.

 

For example, in the article on the liver cancer patient it would surely be helpful if clarification had been provided surrounding the liver overload that occurred near the 10th treatment. Might the authors accept that too much 3-BP was given to the patient? 

[resveratrol_guy]

Perhaps we must accept the fact that monitoring for the destruction of normal cells as opposed to cancerous ones is intractable. (This is basically the limitation of the lysis scanner, not to mention every other known piece of medical technology which might safely be brought to bear on a living patient.)

But then, maybe we shouldn't be drawing this crisp distinction at all, because it seems to boil down to the percentage of glycolytic mitochondria in any given cell. In this sense, no autopsy as currently performed would determine the answer, either.

Fortunately, all this might not matter, to the extent that (1) we can monitor the patient and apply maximum therapy within safe limits and (2) we can, in rapid succession to 3BP, attempt to clean up the "crater" left by the necrotic cancer, and plant stem cells around its inner surface. For example, excise the necrotic "carcass" of a post-3BP liver tumor using positive margin, then spray stem cells all over the inside walls of the hole left behind, which would now consist of mostly healthy cells. It would be like digging up the soil under a former toxic waste site, to a depth of 1 meter below the lowest known level of pollution, then planting food crops on the exposed clean soil.

As to paracetamol, I also wonder if we're just assuming that its synergism is due to glutathione suppression, which in principle could cause energy-starved cancer cells to die of routine oxidative stress which cannot be healed promptly. But this might not be what's happening at all. Maybe it's some other effect of paracetamol entirely. Either way, it needs more experimentation (just like rapamycin and salinomycin) so as mag1 suggested, we can minimize 3BP dosage.

If you want to get ahead of peer review, which suffers some obvious disadvantages as pointed out above, try arxiv.org, which is the world's preprint junk pile. The only thing that peer review accomplishes is to reduce the error rate. That's great, in and of itself, but it must be weighed against the time consumed by doing so. My strong suspicion is that we're better off studying half-baked preprints months before their polished counterparts emerge in publications, many of which end up getting retracted anyway. Of course, patients need to be informed as to the therapist's statistical basis of confidence in any given therapy, which is likely to be weak if the only source was preprint papers.
 

Edited by resveratrol_guy, 08 February 2015 - 05:35 PM.

[mag1]

This is great, the people are coming back! I was worried there was a mutiny afoot.
This topic is too important to be derailed.
3-BP still appears impressive (especially if the toxicity issues are manageable).
I will try harder to be more responsive.

I do not think that I could ethically accept the proposition that any research results with medically relevant
importance to patients that I might discover would be embargoed for a up to a year or more.

Consider the timeline for the liver cancer patient.

-2008: presented at a hospital,

-2008: US 3-BP researchers contacted

-January 26,2009: the first TACE treatment was performed

-February 26,2009: first day of treatment with 3-BP administered by TACE

-February 26,2009 6:00PM: patient leaves the hospital after recovery period

-March 10,2009 (approximately): patient receives another treatment of 3-BP

-March 14,2009 (approximately): patient hospitalized with hepatic coma. This is usually fatal.

-March 14,2009 (approximately): patient returns home and recovers.

-March-November 2009: patient receives 8 more rounds of 3-BP treatment

-December 9,2009: patient succumbs to reported liver overload

-January 9,2012: article received by journal
-January 14,2012: article accepted by journal
-February 11,2012: article published online

Well over ten million people died from cancer while this article made its way to publication.


It might not have been unreasonable to have held a news conference in March of 2009 to disclose the startling results
that had been achieved even at that point. I would have. It could have then been reported that 3-BP had been safely administered three times and a huge anti-tumor response resulting in TLS occurred on the third treatment.

I do not understand how criminal and civil consequences do not apply for the non-disclosure of such medically relevant findings.
Did not the ethics committee find this ethically unacceptable? How can international law be ignored in such instances?

Now in 2015, all these years later, we are still trying to fully understand the results from 2009. With timely disclosure of the initial results, current research would be years further ahead.

[mag1]

Searched arxiv.org.

No results from a search of 3-Bromopyruvate,or 3-BP.

However, the term cancer produced a little over 300 matches.

[mag1]

I am not especially informed about the questions of toxicity, though many current technologies could give some indication of such concerns. For example, the LDH measure gives a reasonably accurate means for assessing whole body tumor burden. This was the primary efficacy biomarker used with the metastatic melanoma patient. The liver cancer report noted that a widely used cancer diagnostic technology is PET scanning which actually is based on overexpression of Hexokinase 2 (from the glycolysis pathway [note relation to 3-BP mechanism]).

The CT scans in Figure 4 of the liver cancer report appear to show the liver tumors. There is some uncertainty as to whether the scan is able to detect liver tumors after 3-BP treatment (due to not using Lipiodol). It is not mentioned in the article whether liver toxicity could be established by simply studying these scans.

It is possible that the liver was chosen as the first test of 3-BP due to its regenerative ability. The article noted that the patient's liver was regenerating and they intended to publish these results.

In the animal studies using direct intra-arterial treatment of the liver, there did not appear to be any toxicity at optimal dosing and method of dosing and no restorative post-treatment was necessary.

We still do not have a good sense of long term safety with IV dosing. The investigators seemed to be quite cautious about systemic dosing even at 1 mg per kg with the melanoma patient. A longer term of observation of this patient would have greatly helped us understand such risk of toxicity. IV dosing would expose all the organs of the body to 3-BP. It would also be very helpful to know whether the paracetamol - 3BP combination is broadly effective in cancer patients.

This is all the more frustrating as articles reporting patients with earlier stage cancer treated with 3-BP have not yet been published. Treating patients before they developed unsustainable tumor masses would reduce the risk and increase the effectiveness of 3-BP treatment.

[mag1]

It has been an ongoing mystery in the scientific community as to why 3-BP does not appear to be more toxic to organs than has been to this point demonstrated. 3-BP is an alkylating agent which would be expected to cause substantial problems associated with toxicity.

The below article explains that the subdued organic toxicity effects of 3-BP at 1.75 mM in rats when given systematically was apparently due to 3-BP binding to serum proteins.

http://www.pubfacts.... in a rat model.

[mag1]

On a closer examination of the above article, it is not clear how the irreversible binding of 3-BP by serum proteins would not also prevent 3-BP from having an effect on the cancer.

It would seem that such a binding might result in a non-toxic, though ineffective drug. (The binding occurs rapidly as noted in the article). However, this is inconsistent with the effectiveness shown with systematic administration in the metastatic melanoma
patient.

"As our findings demonstrate the interaction of 3-BrPA with serum proteins, it is likely that the particular interacting 3-BrPA molecule will no longer be available for further alkylation or toxicity. Further, owing to the irreversible alkylating property of 3-BrPA, it is unlikely that the 3-BrPA might be released from these proteins at later stages to contribute any toxicity."

[pone11]

Perhaps we must accept the fact that monitoring for the destruction of normal cells as opposed to cancerous ones is intractable. (This is basically the limitation of the lysis scanner, not to mention every other known piece of medical technology which might safely be brought to bear on a living patient.)

But then, maybe we shouldn't be drawing this crisp distinction at all, because it seems to boil down to the percentage of glycolytic mitochondria in any given cell. In this sense, no autopsy as currently performed would determine the answer, either.
 

 

I thought that cancer cells show distinct changes to mitochondria.  Specifically the inner folds and membrane of the mitochondria in cancer disintegrates, and the mitochondria becomes a glycolysis factory.   Since the inner mitochondrial membrane is where aerobic metabolism and the electron transport chain reside, I guess that makes some sense.

 

Someone correct me, but in an autopsy couldn't they sample many areas of tissue necrosis, then analyze the mitochondria of those dead cells, looking for the ones that show the telltale signs of cancerous changes?  I'm sure there must be other biomarkers for cancer in the cell that could be tested as well?   How much of this remains stable in the hours or days after death?

[resveratrol_guy]

 

I thought that cancer cells show distinct changes to mitochondria.  Specifically the inner folds and membrane of the mitochondria in cancer disintegrates, and the mitochondria becomes a glycolysis factory.   Since the inner mitochondrial membrane is where aerobic metabolism and the electron transport chain reside, I guess that makes some sense.

 

Someone correct me, but in an autopsy couldn't they sample many areas of tissue necrosis, then analyze the mitochondria of those dead cells, looking for the ones that show the telltale signs of cancerous changes?  I'm sure there must be other biomarkers for cancer in the cell that could be tested as well?   How much of this remains stable in the hours or days after death?

 

 

There's no reason that couldn't be done. I believe you're referring to the cristae mentioned by D'Agostino, which are the interior of the external mitochondrial membranes. For that matter, the inner boundary membranes may decay as well. The problem, though, is that you have a huge tissue volume to biopsy. What are you going to do, sample a cell for every cubic centimeter, then put together a 3D heatmap showing the glycolytic percentage of each cell which survived (or did not survive) therapy? (And how could you ascertain which cells had survived, considering that the cells would overwhelmingly be dead by the time you do an autopsy?)
 

This would be extremely useful data, but it seems very difficult to gather, unless perhaps we could use nuclear magnetic resonance. (Presumably glycolysis involves different ratios of carbon and other atoms as compared to OXPHOS. Resonating with the most popular nuclei in either case might show different intensity levels, allowing us to form a 3D heatmap without lifting a knife. This isn't new thinking; MRI uses hydrogen NMR on a routine basis.)

 

For that matter, why are we using hydrogen resonance with "receptor dyes" to attempt to image cancer? Why not use another form of NMR which looks for glycolysis? Kind of like PET minus the ionizing radiation.

[resveratrol_guy]

Searched arxiv.org.

No results from a search of 3-Bromopyruvate,or 3-BP.

However, the term cancer produced a little over 300 matches.

 

That's not good :(

 

Maybe it means that nothing's in the pipeline, at least from the usual institutions for biotech research.

 

Time for dirty data.

[mag1]

PubMed has almost 20,000 articles listed for cancer in 2014.

arxiv.org appears to be weak in the medical sciences.

[pone11]

User @resveratrol_guy asked me to document my idea to use 3-BP as a method to detect cancer in a new thread.   Here is the thread:

 

http://www.longecity...ancer/?p=713709

 

 

[resveratrol_guy]

I just realized that 3BP might actually be the gateway to mundane stem cell therapy. Please let me explain.

 

The biggest problem with Aubrey DeGrey's "maintenance" approach to longevity is that, among other things, it presupposes that the availability of therapy (and money to pay for it) implies the willingness to avail oneself of it. But, cost issues aside, the first reaction that anyone seems to have to stem cell therapy in general is one of fear -- fear of cancer. I must admit, despite my clear understanding that there is a difference between angiogenesis (proOXPHOS) and pathoangiogenesis (proglycolysis), the idea of jacking up my circulating stem cell population by something like an order of magnitude does actually drain the blood from my face. It takes guts (or insanity, in my case)!

 

What we need as a society is to transition to a world in which stem cell therapy is medically (and financially) mundane. Indeed, the cancer risk is not unrelated to the financial cost: imagine how much it costs to obtain general liability insurance for a stem cell therapy center, for instance.

 

3BP may be the answer. Here's my caveman rationale:

 

Stem cells in 2015 work like this:

 

1. Harvest from bone marrow, adipose tissue, or cord blood.

 

2. Centrifuge them for debris filtration (optional).

 

3. Reinject to target tissue (usually, general circulation or lumbar CSF).

 

Stem cells in 2035 may work like this:

 

1. Harvest from bone marrow, adipose tissue, or cord blood.

 

2. Centrifuge them for debris filtration (required by the Stem Cell Quackery Act of 2029).

 

3. Give the extracted cells a "Warburg bath": set the Warburg threshold to some comfortable value, then fry all the cells which exceed it with the implied dose of 3BP. But realize that because this is done in vitro, we're not giving in vivo tissues any education about 3BP at all! So any malignancies which might reside in the patient remain therapy-naive (nevermind the fact that 3BP may be very hard for cancer cells to evolve around, as it is). And we have a decent shot at achieving a total kill, because presumably any would-be glycopathological stem cells would have been hibernating (because presumably we would have noticed bone marrow cancer or adipose cancer), waiting to cause havoc upon release into circulation. So in order words, we have a few random glycopathological stem cells which just got out of bone marrow prison, so it's time to fry them before they upregulate pathoangiogenesis pursuant to patient reinjection.

 

4. Reinject to target tissue (via DMSO-modulated transdermal sonication because, hey, it's 2035 already).

 

Think about what this would mean, societally. We would transition from "OMG angiogenesis are you nuts?!" to "Which growth factors do I need for next week's triathlon?" Just the attitude shift would be a major step toward an Aubrey DeGrey world.

 

[mag1]

If we're talking about 20 years forward, why not genetically engineer the stem cells so they can't become cancerous?

Apparently, some animal (and people) are genetically protected against cancer. Why not give the stem cells the same advantage.

 

Alternatively, an entirely novel cell surface receptor could be engineered into the stem cells. This might allow minicells to selectively enter these stem cells.   

Or even a molecular computer could be added to the cells which could destroy the cells. if it were determined that the cells had become dysfunctional.

[resveratrol_guy]

If we're talking about 20 years forward, why not genetically engineer the stem cells so they can't become cancerous?

Apparently, some animal (and people) are genetically protected against cancer. Why not give the stem cells the same advantage.

 

Alternatively, an entirely novel cell surface receptor could be engineered into the stem cells. This might allow minicells to selectively enter these stem cells.   

Or even a molecular computer could be added to the cells which could destroy the cells. if it were determined that the cells had become dysfunctional.

 

Well you raise a good point, provided that we can manage to (economically!) replace the patient's lousy mitochondria with those of some Olympic athlete with no familial history of cancer. The problem is that that might only be possible to do on a few cells at a time, considering the complexity of a manual (how could it be automated?) mtDNA transplant across 1000 mitochondria using a theoretical nanosyringe; in this case, the ensuing replication stress incurred by duplicating those cells to therapeutic quantities (perhaps 40 bifurcations) could be significant to the point of outweighing the value of the superior mtDNA in the first place. But yes, it just might work.

 

But I really like this "kill switch" idea! One could imagine a proprietary receptor (made my a nefarious multinational corporation, just like in the movies) dedicated to minicell binding in the event of a catastrophic failure (or, on the positive side, if we learn how to enhance them postimplantation). Then the aforementioned corporation learns how to use them to control people, and we have the basis of a scifi thriller...

 

I think you're talking 2060. A Warburg bath is simpler and dumber.

[mag1]

I was expecting sooner or later someone might try this with 3-BP.

http://pubs.rsc.org/...63f?page=search[open access]

This could really push 3-BP treatment forward.

Figure 3 from the article is somewhat confusing (they do not appear to be using consistent units).
However, targeted delivery seems to give at least 1 log benefit over straight 3-BP.
The units used in Figure 3B are not consistent with Figure 3A. Also, it would be nice to have the
direct comparison on Figure 3B between targeted delivery with and without laser treatment. It is hard to
say but it appears that the laser amps up the effect above and beyond targeted delivery considerably.

Table 1 found that targeted delivery increases effectiveness by 20 times over straight 3-BP!

[mag1]

The article does not seem to provide clear comparisons between the effectiveness of the various treatments
with and without the laser.

In Figure 3B, 3-BP appears to be 3 log more effective in comparison to the same cell type (PC3) in Figure 3A.
The units used in Figure 3B for the other treatments using laser light are not directly comparable to those in Figure 3A.
However, if they matched the benefit seen with 3-BP, than there would be a substantial benefit of the nanoparticles with
laser light over straight 3-BP.

The supplemental tables Figure S8c even suggests that NT-3BP-AuNP is more effective than T-3BP-AuNP.
It is very impressive that 50% of the cells with NT-3-BP-AuNP appear to be end-stage necrosis.

http://www.rsc.org/s...c4sc01963f1.pdf

[tunt01]

  It's true that 3HP downregulated OXPHOS, but this was "In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH)...."    So 3BP attacks the cancer by denying it glycolysis, and naturally since the cancer uses the HK2 enzyme to control activity of the mitochondria, a drug like 3BP that downregulates HK2 is going to selectively deny the cancer access to all energy sources, including OXPHOS.   That's a side-effect, NOT the primary mechanism.

 

 

 

I'm not sure if this has been discussed elsewhere in this thread, but I thought I'd just point out that the beta blocker Propranolol is a Hexokinase II inhibitor, interferes with glucose metabolism, and is widely seen and preventative for cancer.  I believe this is due to it's Beta-2 andregenic blocking effects (it blocks both B1 and B2).  Other selective B2 inhibitors probably have a similar effect.

 

I point this out for anyone who comes across this thread and is looking for some kind of drug (as maybe they are a cancer patient) and might have more interest in something that has already been safely taken by millions of people vs. something unknown and still in development.

 

See:

 

Propranolol inhibits glucose metabolism and 18F-FDG uptake of breast cancer through posttranscriptional downregulation of hexokinase-2.

[mag1]

There was some evidence that Propranolol helped in melanoma.

This might be another agent to combine with 3-BP to amp up effectiveness.

[mag1]

Wow, X-Ray Photodynamic therapy. It's off-topic but worth it.

 

One dose of 0.5 Gy X-Rays eliminated tumors!

 

X-Rays can penetrate deeply into the body.

 

http://cen.acs.org/a...oparticle-Take

[pone11]

 

  It's true that 3HP downregulated OXPHOS, but this was "In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH)...."    So 3BP attacks the cancer by denying it glycolysis, and naturally since the cancer uses the HK2 enzyme to control activity of the mitochondria, a drug like 3BP that downregulates HK2 is going to selectively deny the cancer access to all energy sources, including OXPHOS.   That's a side-effect, NOT the primary mechanism.

 

 

 

I'm not sure if this has been discussed elsewhere in this thread, but I thought I'd just point out that the beta blocker Propranolol is a Hexokinase II inhibitor, interferes with glucose metabolism, and is widely seen and preventative for cancer.  I believe this is due to it's Beta-2 andregenic blocking effects (it blocks both B1 and B2).  Other selective B2 inhibitors probably have a similar effect.

 

I point this out for anyone who comes across this thread and is looking for some kind of drug (as maybe they are a cancer patient) and might have more interest in something that has already been safely taken by millions of people vs. something unknown and still in development.

 

See:

 

Propranolol inhibits glucose metabolism and 18F-FDG uptake of breast cancer through posttranscriptional downregulation of hexokinase-2.

 

 

Nice study, but they lost some opportunities there to:

 

1) Tell us did propanolol have any value as a prophylactic to prevent getting the cancer in the first place?

 

2) Did propanolol extend lifespan in the mice who had cancer?

[tunt01]

 

Nice study, but they lost some opportunities there to:

 

1) Tell us did propanolol have any value as a prophylactic to prevent getting the cancer in the first place?

 

2) Did propanolol extend lifespan in the mice who had cancer?

 

 

RE:

 

1)  I'm not well read enough to know where propanolol has primary preventative effects on cancer.  However, I've seen several papers showing that it is preventative for metastasis, often driven by norepinephrine.  By blocking B2 receptors (which some beta blockers like metoprolol do not accomplish), propranolol inhibits some forms of cancer from metastasizing elsewhere in the body.

 

Example:  Metastasis of prostate cancer via norepinephrine is prevented by propranolol.  migration of pancreatic cancer via norepinephrine inhibited by propranolol.

 

2)  Given the above fact, #2 seems likely to be true (in some instances).  But, I'm not much of an expert on anything cancer related.

[pone11]

 

 

Nice study, but they lost some opportunities there to:

 

1) Tell us did propanolol have any value as a prophylactic to prevent getting the cancer in the first place?

 

2) Did propanolol extend lifespan in the mice who had cancer?

 

 

RE:

 

1)  I'm not well read enough to know where propanolol has primary preventative effects on cancer.  However, I've seen several papers showing that it is preventative for metastasis, often driven by norepinephrine.  By blocking B2 receptors (which some beta blockers like metoprolol do not accomplish), propranolol inhibits some forms of cancer from metastasizing elsewhere in the body.

 

Example:  Metastasis of prostate cancer via norepinephrine is prevented by propranolol.  migration of pancreatic cancer via norepinephrine inhibited by propranolol.

 

2)  Given the above fact, #2 seems likely to be true (in some instances).  But, I'm not much of an expert on anything cancer related.

 

 

Given that metastasis result, why is the drug company marketing propranolol not selling it off-label to doctors as an adjunct to other cancer drugs?   That seems like a huge market for them.

 

The point on 2) was why didn't the original mouse study try to measure that lifespan extension.

[mag1]

Propranolol is a generic drug. There is no money to be made from studying its anti-cancer properties (just like 3-BP).