Some thoughts on 3BP

During the past days I was “forced” to go back to 3BP and think more about it in the context in which I hear more and more about people who are responding but even more important people not responding (out of which some very good friends …).

Actually, when I hear about patients/friends not responding to 3BP, I start to loose my trust in 3BP but than I went back to our file and saw the response so clear in the blood test in our case, during every cycle of 3BP we had (response to one cycle even visible on CT). And than the trust comes back and with that the question WHY? [Note, now we are using Diflunisal (next to many others including some immunotheraphies), which seems to show response. After the Diflu cycle, we will probably go back to 3BP if appropriate and depending on what my wife likes]

In the end, we are battling the challenge of humanity, i.e. cancer. Fighting in a field where the conventional medicine of this world could not help us … and so far successfully.

Back to the question WHY. I know that this question is constantly in the mind of some great scientists involved in the 3BP research. Why some people are responding and some not? Of course, there can be so many explanations, that include blood type, tumor perfusion, MCT expression, 3BP administration strategy and stability of the specific formulation … and so on … However, I feel the main answer is connected to the following statement I came across while reading some patents on Diflu: “Thus each type of tumor has an intrinsic average intercellular pH, which, for example, in the case of breast tumors is about 6.7 and in the case of colon tumors about 6.9.” Ref

The interesting point is that this statement or piece of information may be the right link between two facts:

  1. A pattern that seems to emerge from all the outcomes we hear of following 3BP treatment, i.e. most of the responding patients are breast cancer patients. (And many of which are simply using the oral administration strategy mainly.) Next to that one prostate, one melanoma, one adrenal, one lung, one pancreas, two liver (but these liver cases were TACE which may be seen as forced and direct administration and should not be compared to the others – my personal opinion). I am not sure about others but at least this is what comes to my mind in terms of most relevant cases.
    .
  2. Recently, we have seen an article published stating that 3BP transport is higher when the extracellular milieu is acidic:
    The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH:At pH6.0, the affinity of cancer cells for 3BP transport correlates with their sensitivity, a pattern that does not occur at pH7.4. In the three cell lines, the uptake of 3BP is dependent on the protonmotive force and is decreased by MCTs (monocarboxylate transporters) inhibitors. In the SK-BR-3 cell line, a sodium-dependent transport also occurs. Butyrate promotes the localization of MCT-1 at the plasma membrane and increases the level of MCT-4 expression, leading to a higher sensitivity for 3BP … We find that the affinity for 3BP transport is higher when the extracellular milieu is acidic. This is a typical phenotype of tumour microenvironment and explains the lack of secondary effects of 3BP already described in invivo studies [Ko et al. (2004) Biochem. Biophys. Res. Commun. 324, 269-275].

Yes, while it needs to be investigated further, it is probably the extracellular pH that makes the difference. And breast cancer seems to be one that is characterized by an even lower extracellular pH and this may facilitate the transport of 3BP inside the cancer cells. What are the other cancers characterized by an more acidic tumor environment? That remains to be further investigated. However,this could be a way to select patients that are likely to respond to 3BP treatment. Since the extracellular pH is inverse proportional with the glycolysis (i.e. the higher the glycolisis, the lower the extracellular pH will be) a simple way to identify potential respondents to 3BP is to use PET scan intensity as a reference (however, as discussed here, we need to remember that in my view besides low extracellular pH there is a need for Oxygen as well in order to have the cancer cells able to be fueled by lactate).

Yes, MCT transporters are highly dependent on pH. Transport rates are increased over 10-fold by lowering the pH one unit from 7.4 to 6.4. (Ref.) And as we know, the transporters used by 3BP to enter the cancer cells are the MCTs.

As discussed in other 3BP-related articles on this website, getting response is the first challenge. Maintaining that is another challenge that needs to be addressed together with other drugs, including angiogenesis inhibitors and glycoinhibitors.

Other references:

Cellular pH Gradient in Tumor versus Normal Tissue: Potential Exploitation for the Treatment of Cancer

Disclaimer: https://www.cancertreatmentsresearch.com/?p=1735

Related Articles


49
Leave a Reply

Please Login to comment
avatar
  Subscribe  
Notify of
Fred
Member
Fred

I have a supply of 3BP in the fridge waiting for me to figure out how to utilize it in my wife’s ovarian cancer therapies. Her cancer lurks in the abdomen with numerous mesentery implants of concern. We’ve kept it at bay 6 1/2 years with various chemos, HBOT, IVC, ketogenic diet, supplements, off-labels and on and on but it’s still there.

I initially thought IV 3BP might be the way to go but never understood how it could survive the long trip through tightly regulated, slightly alkaline blood. Lately, and after reading your recent thoughts, I think oral and topical might be more appropriate. I believe the path from stomach to colon is acidic to very acidic. We’re constantly aware of how close the cancer is to the GI tract and with my limited grasp of how the 3BP would be utilized, I like the fact it can go straight to the cancer’s neighborhood.

One other point. To date I’ve piled on more and more therapies as the years go by, driving my poor dear wife a little crazy with it all. I like the way you seem to vary the attack, dropping one therapy as you start another and then going back. I’m going to be looking at that.

Bernhard Nagel
Guest

What about cannabis oil? I am seeing more people using it effectively than any other protocol.

Christy
Guest
Christy

Where does one get 3-BP? I have a similar story with Ovarian Cancer, 5 years.

Fred
Member
Fred

Daniel, I’m still trying to decide on which way to go with 3BP. My wife recently developed shingles, disappointing because her tumor marker was quickly dropping under a new half-dose Taxol regimen. We had to shut down chemo for three weeks. During this time she developed a good amount of ascites fluid in the abdomen. We don’t know if it is a product of cancer or the shingles. If it is malignant ascites it is not good sign. We need to quickly become more aggressive.

If we administer 3BP orally it will go straight to the stomach/GI. From there the path of 3BP to the abdominal implants and ascites is a mystery to me. Frustrating because the cancer is in the abdomen, inches away. I’m an audio engineer but not afraid to ask very stupid questions. You’ve presented an oral administration which seems very straightforward and topical/DMSO which is also interesting. Would these two methods have a chance or do you see IV as the most efficient approach. I am setup to do IV-3BP, HBOT, IV-C.

Reading your thoughts above I wondered about the ovarian tumor cell environment. While the following paper is more concerned with imaging, it seems to suggest it the ovarian tumor intracellular pH is >7.0 and the extracellular pH is <7.0, potentially good for 3BP:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533099/

I have a tentative 3 week 3BP cycle I can email if you're interested. As always, I'm looking for any quick thoughts you might have (I know you have your own battles).

tomkb
Member

Daniel,
I like your theory on pH. I also would like to re-emphasize one of the possibilities you’ve pointed out: MCT1 expression levels in different tissues. You can find it online (free access) Nature Genetics, 45:104-108. Birosy et al. MCT-1mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors. The data is in the supplemental section.

tomkb
Member

Fred,
You can do both, i.e, one followed by another with a few hours of rest or supporting measures in between, e.g., the HBOT you have in your garage or high dose vit C. It’s been done before.

Jurgen Daub
Guest
Jurgen Daub

has any body used 5BP for lymphoma or leukemia?

Jurgen Daub
Guest
Jurgen Daub

sorry, should be 3BP

Jcancom
Member

Hey, Jurgen.

3-BrOP is highly similar to 3-BP ( it simply adds a few carbons on one end).
3-BrOP has been found to be quite effective with leukemia and lymphoma.
It is not clear whether MD Anderson intends to move it forward.

http://www.cancercuremedicine.com/news-md-anderson-3-brop-or-glycolysin.html

Sylvia Smith
Guest
Sylvia Smith

Dear Daniel,
I would like to request your ideas and help concerning the use of 3BP for High Grade Serous Ovarian CA . Diagnosed 1 1/2 years ago-numerous surgeries, 6 months chemo with Gemzar and Cisplat. Just had large incisional hernia repair. Went back for 1 month follow up to learn 2 areas were showing tumor growth/enlargement. One in the left subphrenic area and one above my belly button near the peritoneum. I believe the 3BP may hold promise. Doc at MD Anderson recommends starting more chemo but I am hoping to do something less toxic. What would be the best delivery? Are there any DR.s anywhere in the world you could recommend that could actively treat me? Do you know of any HGSOC patients who have been treated successfully? Thank you.

Dana
Guest
Dana

Hi Daniel,
Thanks for your research. Do you have any more information on whether Dr. Ko is beginning clinical trials? I have emailed her but have not heard back yet. And along those lines, do you know if it has effectiveness with treating multiple myeloma? Thank you again.

W.
Member
W.
marcosbomber901
Member

Hi Daniel
in the preparation IV of 3BP does not put you may need a PH meter;¿because the mixture with the correct quantities has a ph
suitable for intravenous infusion?.Does it occur the same in not buffer version?.thank you

Jcancom
Member

D, I have been looking everywhere for the CAS number for radiolabeled 3-BP.
Might you know this?

Jcancom
Member

D, I think I posted about this about a year ago on the compass thread. I was surfing around some of the chemical houses and I stumbled onto a radiolabeled 3-BP with a CAS number. I was fairly shocked. Was there really demand for such a chemical? My guess is Yes. From what I remember this was just plain 3-BP
with one of the carbon atoms replaced with C14. Actually now that I think about it, it occurs to me that this might have been in one of the 3-BP patents.

This has me super excited! 3-BP has been out there for 20 years and it still has not really got very far. There have been some very large responses, though others do not have such responses. What I think would help
so much is having a biomarker that could prospectively identify those patients that would have super responses.

I am not sure how the radiochemistry works, though the game plan that I have is to give something like a radiolabeled 3-BP or lactate and then do a PET/CAT (whatever) scan and see if the entire tumor mass would light up. With the liver patient and the melanoma patient, such scans would have clearly shown that they would be Super-responders. The great part about this is that with the melanoma patient he actually did not
respond at first; it was only when they added in the paracetamol. Yet, with the 3-BP scanner, the response would still be highly predictable because all you need is for the radiolabeled 3-BP to enter via MCT-1.

What is also fairly interesting about this is that it perhaps could be done under the radar. A patient could go
in for a fairly routine scan, use the existing infrastructure and possibly determine that they were super responders.

The idea here is that 3-BP would then have a very large amount of momentum to be approved under an orphan indication. The argument that has been ongoing about 3-BP could then no longer continue.

D, what do you think? I believe that finder has been thinking and working to move this idea forward quietly,
though it might be good to start a conversation about this.