Monday, 16 November 2020

Blockade Strategy Feedback

 Hello, everyone!

I was diagnosed in May 2019 with GBM and I have completed SOC in Apr. 2020 (Total resection, 42days Chemo/Radiation, and 6 months maintenance chemo). I have done a lot of research on supplements and medications as well as reviewing many promising techniques to stop GBM. One, in particular, had caught my eye which is the CUSP9 protocol. I like this protocol because it attempts to stop GBM in its tracks not just slow or delay things until a recurrence. In addition, I find the results from this study to be one of the best and I believe the strategy used to attack a recurrence is very logical by blocking all the known survival pathways of GBM. I feel that current strategies only partially attack GBM and because of its adaptive characteristics only delays or slows down the inevitable. Cutting off survival paths seems the best strategy until something more profound is developed for people with GBM.

I devised this because it is a helpless feeling treatment is over without much to prevent a recurrence, cocktails are either partially attempting to stop GBM or there is no rhyme or reason to them, dosing strategies do not follow the research, and posted research used in cocktails does not come from peer-reviewed information.

I do not have access to prescription drugs like some people to be able to copy the CUSP9 protocol if I ever have a recurrence or for the newly diagnosed protocol. So I tried researching supplements to see if I could find a supplement-based comparable solution. Unfortunately, when supplements are tested in studies, there is little information on the survival pathways impacted by supplements in the study. I had to reassess my strategy at this point.

I did notice supplements did have common terms in the studies such as proliferation, apoptosis, etc. So I went through many studies and found 9 common mechanisms referenced in the studies as shown.

So I went through studies (NCBI) on many popular supplements used in many "cocktails" and identified the mechanisms impacted by the supplements. I came up with this:

I chose a list of supplements which should provide a blockade to all the mechanisms. I also chose redundancies of each mechanism as I suspect there are many pathways behind these mechanisms. To give a validation to my blockage strategy, I researched Ben Williams protocol he uses to see what mechanisms his protocol covers. I was surprised to find this

His protocol impacts all the mechanisms I found and he also has redundancies in each mechanism of the blockade.

Another argument for this is my oncologist informed me in March of 2020 I had a tumor remnant leftover from surgery 2.5cm in size at the largest diameter with no metabolic activity(contrast and spectroscopy). He thought it was swelling but the MRI with spectroscopy verified as a tumor remnant. This was a shock because I was told by the surgeon I had a complete resection. I was told the only way to get rid of it was removal during any additional surgeries I may experience and since there was no metabolic activity, it would be monitored. In my July MRI, the remnant was 1.8cm in size with a "significant" reduction in blood flow to the original tumor area. In my last October MRI, it was at 1.0cm with more "significant" reduction in blood flow (no metabolic activity). 

So my questions are these:

1. My oncologist attributes the reductions to SOC. However, he admits never seeing such a positive result as this. Could this be the result of SOC, my blockade, or something else?

2. Does anyone see limitations in this or recommend improvements?

Thank you for your feedback.




  1. Hi Eric,
    Your commitment to organized research is commendable. Glad to hear something has been working for you and that the tumor remnant continues to shrink!
    1. Of course, the oncologist is always going to attribute any improvements to the SOC, we can just take that as a given, whether true or not. Ben William's doctors said the same thing, though he is convinced if he had simply listened to his doctors and done nothing else, he would not be alive today. There are far too many unknowns to say whether any given cocktail is going to work for any given individual. The important thing is to try, and you may get lucky and stumble upon the right formula out of some combination of sheer luck and hard (research) work. If you are having good results in your scans, probably a good idea to keep doing what you're doing.

    What kind of testing was carried out on your tumor tissue? Was it tested for IDH1 mutation? MGMT methylation? EGFR amplification?

  2. The theory behind CUSP-9 or Ben Williams' approach is completely sound in my view. The difficulty is the implementation. So much of the research is based on cell culture studies, where isolated cells in the lab are exposed to drugs or natural products, quite often at concentrations that could not be achieved in humans without serious toxicity. I very rarely even take the time to read a study that is based only on cell culture, unless they can show that the drug concentrations used in the lab are comparable to levels of free drug in human plasma after standard dosing regimens likely to be used in practise. Rodent studies would appear to be a little more translatable to humans, in the sense that they cannot give drug doses so high that they kill the animal with unwanted drug toxicities (there is no such limitation in cell culture work). Even then, rodent studies don't have the greatest track record translating to humans, but at least they show potential mechanisms that might be in effect with physiologically achievable drug levels.

    Getting enough drug from the bloodstream into the brain tumor tissue is yet another matter. Cell culture studies bypass this issue completely. Many rodent studies also bypass this problem by using flank models of glioma, where a glioma cells are implanted into the flank of an animal, rather than "orthotopically".

    I really feel that a big part of the problem in brain tumor therapy is pharmacokinetic in nature, in other words the drug might be effective in the lab with isolated cells, but in actuality you have to first get enough of the drug into the bloodstream in free, active form (drugs with high bioavailability), and then cross the second hurdle of getting enough of that drug from the bloodstream across the blood-brain barrier. Yes the BBB might be disrupted to some extent in the center of a fast growing tumour (the part most likely to be resected surgically), but in diffuse glioma there are always glioma cells in the periphery protected by a fully intact BBB. So you really need drugs with high bioavailability and good crossing of the blood-brain barrier. It is interesting to research drugs known to have effects in the central nervous system, such as fluoxetine (Prozac) and sertraline (included in CUSP9 if I recall correctly). I have a feeling that many of the nutraceutical supplements are getting into the central nervous system in only trace amounts, if at all. But it is also likely that some do.

    It is the same problem trying to repurpose oncology drugs designed for other cancers to brain tumours. The drug's mechanism might be very useful, but if not enough drug gets to the target, it is not going to make a difference.

    That said, if I was seeing results like you are, I would probably continue to do what I had been doing and maybe add on to that.
    Finally, there is some evidence of Accutane (13-cis retinoic acid, or isotretinoin) as having a use as a maintenance therapy after the completion of all chemotherapy cycles.

    I think it's more likely to get a doctor to write a single off-label prescription, than more than one, let alone an entire cocktail list. If you could find a doctor willing to help you with one prescription, they might be willing to write another one later if everything is going well.

    All the best of luck to you!

  3. Hello Stephen!
    Thank you for your response! I agree with you on the hurdles with this disease. However, I have been able to see some things work. For example, I wanted to get my blood glucose levels into the 70-80mg/dl range. My baseline was averaging 105-120mg/dl. I used Berberine to lower this down and, based on studies, I predicted on my size about 900mg of Berberine should get me there. I took one Berberine pill (500mg) per day and saw my glucose dropped to the 90-105mg/dl range. I started taking 1000mg and this got me into the 75-85 range I wanted. So the study, in my opinion, was correct and verifiable. I just used this dosing calculator here:

    If any study is based on an animal, I calculate the conversion from this here:

    It definitely seemed to get me in the ballpark on a few supplements. So there appears a correlation from studies to real world that I can verify but I do agree there are the limitations from absorption, BBB, and other factors for other medications/supplements. This is why I employed multiple redundancies under each mechanism in the hopes something gets through. It's not an exact science but it seemed I needed to develop a good foundation and get the dosages correct. It seems people are just copying off each other and dosages are determined on the "more is better" idea instead of calculating dosages based on their size from the study.

    I have unmethylated/wild type. genomic instability with partial mosaic losses of 1p, 19q, Chr 7 mosaic amplifications including EGFR amplification, CDKN2A and PTEN mosaic losses. I have not looked up what all these mean outside of MGMT and IDH. Perhaps you know.

    Thank you again for your responses!


    1. Yes I agree with all that. I have definitely spent a fair amount of time trying to convert animal doses into human doses. I later realized that this was a very broad, imperfect, ballpark kind of approach, but in the absence of human studies it is what we have to work with.

      It sounds like they're using the word mosaic to mean subclonal alterations that are only occurring in a subpopulation of the cells. EGFR is the most commonly altered gene in non-IDH types of adult GBM. There have been numerous drugs developed in other cancers targeting EGFR, but none have had consistent enough success in GBM trials to get full approval for that indication. (dacomitinib trial 2017) (osimertinib review, 2019)

      CDKN2A is a gene that produces a protein that inhibits a cell's progression through the cell cycle. It is one of the most commonly deleted genes in GBM, either "hemizygous deletion" (one copy lost), or "homozygous deletion" (both copies lost).

      PTEN is another tumor suppressor that directly counteracts proliferative signaling in the PI3K/Akt pathway. This gene is location on chromosome 10. Most adult GBM's (non IDH-mutant) have lost one copy of chromosome 10, leaving only one copy of PTEN intact. Very often this remaining copy is mutated (about 30% of non-IDH GBMs have a PTEN mutation) in these cases effectively leaving no functional PTEN, and overactive PI3K/Akt/mTOR proliferative signaling.

  4. Hello Stephen,

    Thank you for taken the time to comment and give feedback! It is much appreciated!

    It gives me more to digest (insert bio-available pun here" and think about going forward.