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How fast can cancer adjust (metabolically) to repurposed drugs ?

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MichalH
(@michalh)
Joined: 3 years ago
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There is a lot of talk about starving cancer and blocking its metabolism by blocking all the pathways. In the case of my mum (and many others) I think it is not possible to block all the pathways because my mum cannot take some of the needed drugs (she started loosing too much weight on metformin and other supplements). So I am trying to figure out some other strategy.  


   
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MichalH
(@michalh)
Joined: 3 years ago
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Topic starter  

I wanted to write a longer post, but somehow posted it and it seems it  cannot be edited - so here it is again:

There is a lot of talk about starving cancer and blocking its metabolism by blocking all the pathways. In the case of my mum (and many others) I think it is not possible to block all the pathways because my mum cannot take some of the needed drugs (she started loosing too much weight on metformin and other supplements). So I am trying to figure out some other strategy.  

My mum has EGFR positive lung cancer (NSCLC) and also PIK3CA mutation was found last year after progression (the cancer has been progressing slowly for about a year now).  At the moment my mum is taking melatonin (100 mg), curcumin+EGCG, astragalus (these should block glycolysis+PIK3CA), mebendazole, silibinin (for brain mets) along with her conventional treatment which is a TKI inhibitor afatinib. 

After diagnosis my mum took afatinib for 2 years, than she had a  limited progression and itwas stopped and she had a couple chemotherapy infusions and tried another TKI and also had a period of no treatment (with overall progression).  After 6 months we introduced afatinib again and it has worked decently since then for about 1,5 year (with slow overall progression).

So we basically experienced a moderately succesfull retreatment with afatinib. Which makes me wonder whether similar  strategy  could be applied for repurposed drugs and supplements. I had a feeling that some of them worked for my mum when I introduced them, but later they might have lost their effect (eg berberine ..). Therefore maybe taking them not continuosly for a long time but rather with breaks or switching between various drugs would help prevent  the cancer adjusting to them and creating resistance ? What do you think??

 


   
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Daniel
(@daniel)
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HI Michal H,

Thank you for your comment. Indeed, it's difficult to block all pathways and I do not believe in this approach as we actually do not know all relevant pathways in general (some still remain to be discovered) and even if we would want to address all we know it is not possible to also address them successfully as addressing each pathway requires high dose of supplements and drugs and multiple supplements and drugs for each pathway (at least two). This is why I believe in identifying bottlenecks in cancer and address those as intensive as possible. I discussed this here https://www.cancertreatmentsresearch.com/shutting-down-the-power-house-of-cancer/

Besides that, I totally agree that another relevant dimension is drug resistance. On this line, I think switching from time to time an effective treatment or cocktail makes very much sense. For example a switch every few months. In reality it is so difficult to do the switch once you see something works. And this is the biggest challenge I think. But if we can do that, I think that is a good idea when we are dealing with slow progressing cancers. However, wen we deal with very aggressive cancers, I would better stay with what works.

Kind regards,
Daniel

 


   
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MichalH
(@michalh)
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@daniel Hi Daniel, thank you, I knew you said it is difficult to block all pathways in your earlier article and it is definitely the case for my mum. 

 


   
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MichalH
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What do you think how long it takes for cancer to chance its metabolism? They say (Jane McLelland) that if you block glucose then cancer switches to getting the energy from glutamine and other sources. But how long this actually takes ?


   
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johan
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@michalh

I don't know if there's an aswer to that question, cell population in a tumor is very heterogeneous, and is different from one individual to another.

 


   
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Daniel
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@michalh I agree with Johan.

But to answer to your question, I expect this happens very fast, in a matter of days. Just think about how much it takes the brain to switch from glucose to ketones when starting ketogenic diet.

Kind regards,
Daniel

 


   
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asafsh
(@asafsh)
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Posted by: @michalh

There is a lot of talk about starving cancer and blocking its metabolism by blocking all the pathways. In the case of my mum (and many others) I think it is not possible to block all the pathways because my mum cannot take some of the needed drugs (she started loosing too much weight on metformin and other supplements). So I am trying to figure out some other strategy.  

Hi Michalh

The article whose link was posted on this site had some points to add-on additive recycling to avoid tumor  resistance buildup. I can't validate whether it's true for your case or not.

The recycling information isn't clearly present in ReDO related articles posted here and it would be good if strategies described there will include this information (based on available evidence of course).

Below is excerpt from that article:

"Beneficial effect of additional treatment with widely available anticancer agents in advanced small lung cell carcinoma: A case report"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256253/

"Simultaneously, an off-label therapy was administered. The individualized scheme included curcumin, parthenolide, betuline, sulforaphane, withanolides, lactoferrin, pomegranate fruit extract, flaxseed orally and dioscorea in inhalational form.
The treatment strategy was based on changing the agents every 5 days in order to avoid developing resistance to treatment."

Looks like authors do have some experience in off-label drug administration and it is worth to contact them directly (better if your physician will do) for further clarification. 

 


   
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MichalH
(@michalh)
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Topic starter  

Thanks a lot to all of you for your replies! So it seems that metabolic adjustment could be  pretty fast (a couple of days) whereas resistance caused by other mechanisms takes more time (weeks/months/years)  ?

asafsh - thank you for sharing the study, really interesting, success with SCLC is rare. It could  be helpful to hear the researchers comments and reasoning for the drug choice and change frequency.  The person was taking also metformin and atorvastatin all the time that might have contributed. 


   
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johan
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@michalh

Inhibition of tumor metastasis by targeted daunorubicin and dioscin codelivery liposomes modified with PFV for the treatment of non-small-cell lung cancer.

https://www.ncbi.nlm.nih.gov/pubmed/31239668


   
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MichalH
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@johan  thank you Johan. Sorry for the delay in my response,  I have been rather busy recently in these turbulent days and also mum has pneumonia, so needed to focus on the fight with pneumonia. The paper you link is rather technical and hard to understand for me, but it seems that the agents used would be extremely difficult to source.  Or are they available in some form or is there anything available with similar effect ?   Thank you.


   
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johan
(@j)
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@michalh

I'm sorry that study wasn't of much help. 

Have you looked into Honokiol?

For example in combination with chloroquine:

https://pdfs.semanticscholar.org/4666/1b43e9a442a5760e86eb5ee8b752eb6d43f3.pdf

In combination with Modified Citrus Pectin.

In combination with Artemisinin

 

 

 


   
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John R.
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@michalh I disagree with Daniel as blocking the major pathways successfully is possible as evidenced by Jane McLelland's and other people's success. Of course, in different kinds of cancers these pathways are different but not in way that you can't identify them. For SCLC, you would need to block all the major pathways mentioned in McLelland's book, she identifies them and explains how they can be blocked. 

Specifically for SCLC (but also for other kinds of cancers), you might also want to take a look at Joe Tippen's protocol (which is based on fenbendazole) with which he healed his highly metastasized SCLC. For more information, please read his story to the very end: https://www.mycancerstory.rocks/single-post/my-story-part-1-start-here . You might also want to take a look at his FB group mentioned in the above link. 

All the very best for you and your mum. There is always hope and a way. Keep searching!


   
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Daniel
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@john-r Dear John,

Thank you for sharing your view.

Finally, nobody knows 100% what is the best way to address cancer, but there are some good ways we have identified to help improve and extend life. Jane's approach is one, more advanced, while John's approach is another one, more basic I woudl say. I believe both can be effective in some cases. But I also believe we need to use the knowledge available and our logic, to try to either advance those perspectives or see other perspectives.

My above statement was related to the fact that we need to choose our fight in order to increase the chance of effectiveness, instead of fighting on many fronts at the same time. And if we have more resources to deploy, we can extend our fight on other fronts besides the main one we selected.

On this line, if you read the latest version of Jane's book, you could see that she is moving towards such an approach when she is focussed on ferropotosis. Joe's approach, it's another example of a focussed approach.

Nevertheless, I like to keep my mind open and also realize that there is one important perspective, through which a more "unfocussed" fight can make more sense vs. a focussed one. Let me explain what I mean:

1. If the origin and the driver of cancer is at the tumor level, including e.g. cancer stem cells, viruses, parasites, fungus, bacteria, or even hormonal, a focussed strategy makes sense. Why? Because the first priority is to address the main mechanisms, effectively, with high enough doses. In other words, you need high doses of supplements or drugs to reach the blood stream and finally reach your targets. Therefore, the priority will be on specific drugs and supplements since it is not practically possible to push a wide range of supplements and drugs, each at high dose.

2. If on the other hand, the origin and the drivers of cancer is at microbiome level, the story changes. That is because the microbiome can be reached in most of the cases with much lower doses. In this case, we can use many supplements and drugs at low dose. But in this case, we do not speak anymore about intracellular pathways to address in relation to the tumor and its environments.

While Joes and Janes success stories can be explained under point #1 above, it may very well be that the success came by luckily addressing effectively point #2 above.

As a side note, I did share the story of Joe in a post https://www.cancertreatmentsresearch.com/fenbendazole/

One success story that I think could fit to point #2 above is this https://www.cancertreatmentsresearch.com/a-silver-bullet-to-kill-cancer/

In this case, a patient succeeded to get in complete remission (dealing with a cancer that was spread allover the body) in about 3 months, with colloidal silver alone. After such great results, the doctors checked the solution he used and that contained 3-12 nm silver nano particles. However, when checking the blood stream, they could not find any nanoparticles, after drinking his solution. That means that the whole effect he obtain was possibly via the effect on the microbiome (with impact on the immune system) and not by getting the nanoparticles to the tumor location.

I hope one day, I can write a post on this subject #2 above.

Kind regards,
Daniel


   
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medline
(@aliml2)
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In my opinion, especially in the case of lung cancer, we should first start by blocking the production, transport and storage of serotonin!

Lung function – Metabolic

The lungs perform several metabolic functions including gas exchange, conversion of angiotensin I to angiotensin II by angiotensin converting enzyme (ACE), inactivation of vasoactive substances, and protein synthesis.

Angiotensin converting enzyme is found on the surface of capillary endothelial cells in the lungs. The enzyme catalyzes the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor.

Many vasoactive substances are also inactivated during passage through the lungs. Bradykinin is inactivated by ACE. Serotonin is also inactivated in the lungs, not through degradation, but rather through uptake and storage. The lungs also contain enzymes that degrade prostaglandins E1, E2, and F2alpha, as well as norepinephrine.

The lungs are involved in immune function through production and secretion of IgA. The lungs also perform synthetic functions including formation of phospholipids, which form surfactant, as well as collagen and elastin protein synthesis.

https://openanesthesia.org/aba_lung_function_-_metabolic

Serotonin is produced and released by the gut as well as the stomach, stored and transported by platelets, and absorbed and stored in the lungs. Therefore, reducing peripheral serotonin, inhibiting serotonin synthesis, blocking serotonin receptors and anti-platelets are the first line of lung cancer treatment. In the next step, norepinephrine blockers and bradykinin inhibitors, antiprostaglandins, antihistamines, etc. can be added to the treatment.


   
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