It is well know that tumors often develop resistance to (chemo) therapies via various mechanisms. Some of the mechanisms are well understood today and there are various drugs or supplements that may have the ability to suppress some of these resistance mechanisms. Bellow, I tried to cover most of the known resistance mechanism and indicate drugs or supplements to address them. In order to maximize the treatment outcome, I would use one element from each of the following categories. In general, I would probably use them about one week before the chemo, during the chemo and some days/weeks after chemo.
Based on the categories mentioned below, here is a nice cocktail:
- Palmitoylethanolamide – 3 x 400 mg/day – (supplement)
- Pyrvinium pamoate – 5 mg/kg/day – (over the counter in countries like Sweden, Norway, etc.)
- Scorpion Venom – (supplement)
- Omeprazole – 40 to 80mg/day – (over the counter in countries like the Netherlands, Belgium, etc.)
- to use only if the chemo used is weak basis – if it is weak acid I would not use Omeprazole and stop all proton pump inhibitors during chemo as the weak acid chemo effectiveness may be lowered by proton pump inhibitors.
- Verapamil – 3 x 80mg/day – (on prescription or online pharmacies)
- Dipyridamole – 2 x 200mg/day – (over the counter in countries like Belgium, etc.)
- Metformin – 2 x 500mg/day – (on prescription or online pharmacies)
- Chloroquine – 200 to 400mg/day – (over the counter – for those traveling to countries with malaria risk)
- Doxycycline – 200 to 400mg/day – (on prescription or online pharmacies) and or Mebendazole 200mg – 1g/day (this is one of my favorites – over the counter and available on eBay)
- Omega-3 (EPA and DHA) – 10g-15g/day
Note: The list bellow will be continuously updated and refers to various elements that if used prior or during the chemo sessions may enhance the effectiveness of the chemo.
Update 08.03.2016: Dear All reading this website, based on recent personal experience I suggest that while using chemo the strong anti oxidants (such as Alpha Lipoic Acid, NAC, etc.) shoudl not be used in high dose forms such as Intra Venous. Not even several days after or before chemo as they will clearly protect cancer cells. I know that this is what the oncologist are saying and many are questioning this statement but now I support 100% that statement. Low dose oral supplements such as Alpha Lipoic Acid may help and support e.g. the liver (so I may still use that?) but high dose will help cancer cells defend the pro oxidant anti cancer effect of chemo or other pro oxidant treatments such as 3BP.
- Palmitoylethanolamide – Reducing Pain and Providing Neuroprotection (Ref1, Ref2, Ref3) also anti angiogenesis and control of mast cell activation.
Dose: 3 times 400 mg/day
Reducing Glutathione – Glutathione (GSH) is the most abundant non-enzymatic antioxidant molecule in the cell and is essential for cell survival and redox homeostasis – Glutathione is used by cancer cells to compensate for increase oxidative stress due to treatments such as chemo or radiation
- Ethacrynic acid – glutathione transferase inhibitor
- Pyrvinium pamoate – reducing GSH supply (not Cystein) from stromal cells http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538400/
- Sulfasalazine – reducing Cystein
- Scorpion Venom – blocks annexin A2 and as a result reduces GSH and increases oxidative stress
- Omega-3 – will push GSH out of the cell
Therefore, during Chemo we need to avoid strong anti oxidants such as IV Alpha Lipoic Acid or NAC supplements. To me that doesn’t mean that we need to avoid food with anti oxidant properties.
“Cancer cells have a high demand for ATP because it provides the ‘fuel’ for aberrant proliferation. However, the dark side of this uncontrolled energy production is the accumulation of ROS, which needs to be counteracted by scavenging mechanisms to ensure cell survival. At high levels, ROS promote cell death and severe cellular damage. Cancer cells need to combat this high levels of ROS. Therefore, cancer cells characteristically have a high antioxidant capacity that regulates ROS to levels that are compatible with cellular biological functions but still higher than in normal cells. We believe that targeting these enhanced antioxidant defence mechanisms may represent a strategy that can specifically kill cancer cells.” (Ref.)
“ROS are broadly defined as oxygen-containing chemical species with reactive properties. These include the superoxide (O2 •−) and hydroxyl (HO• ) free radicals as well as non-radical molecules such as hydrogen peroxide (H2 O2 )” (Ref.)
“Thus, although treatments such as chemotherapy and radiotherapy — which induce the production of ROS — are useful for eliminating the bulk of cancer cells, such approaches may fail to cure the patient owing to the superior ability of cancer stem cells to survive in conditions of high ROS by upregulating levels of antioxidants. As ROS are critical mediators of the lethal effects of ionizing radiation and some anticancer drugs, TICs may be preferentially spared and actively selected by treatments that depend on high ROS levels.” (Ref.)
Reducing acidity around the tumors – most of the tumors are using glucose as one of the main fuels for energy production. During this energy production, acidity (protons) are being produced and continuously pushed out into the tumor environment, via several types of transporters, creating an acidic environment. This environment promotes tumor progression, inhibits the action of the immune system and “deactivates” various chemotheraphies that are weak basis (but is helping the weak acid chemos). Various elements that lead to reduction of acidity around tumors:
Therefore, I would check if the chemo I use is weak basis and if yes I would consider this approach to increase its effectiveness. If on the other hand is weak acid, I would stay away from combing proton pump inhibitors with the chemo.
Reducing Multi Drug Resistence – many cancers can resist chemotheraphy due to specific pumps that are located in the cell membrane and are used to push the drugs out of the cells. These pumps are over expressed in cancer. Various elements that can reduce or inhibit these pumps are:
- Verapamil (e.g. Ref.)
- Note: Coadministration of simvastatin (or lovastatin) with antifungals (itraconazole or ketoconazole) can result in rhabdomyolysis and acute renal failure (Ref.) Simvastatin & lovastatin should therefore not be used concomitantly with itraconazole and other potent CYP3A4 inhibitors, or the dosage of lovastatin should be greatly reduced while using a CYP3A4 inhibitor (Ref.). This increased toxicity is not apparent with fluvastatin (Ref.)
- Tetrandrine (this is a natural Ca channel inhibitor – cheap – used in China before and during Radiotherapy and Chemo to enhance the effect of the therapies – I very much like it)
- Mebendazole was recently found to inhibit MDR (Ref.)
Increasing blood flow – tumors usually have leaky blood supply and that limits the chemotheraphy that may reach the tumors. Various elements that can help dilated the vessels are:
Reduce glucose to cancer cells – reducing glucose available will lead to lower energy in the cancer cells available to fight chemotheraphy. Below are a few elements that can help reduce the glucose availability of energy production:
Increase RedOx – chemotheraphy puts constant stress on the cancer cells and there are other theraphies who can further add additional stress next to that:
- DCA (Dichloroacetate)
- Scorpion Venom
- Exercise & Oxygen
Inhibiting Autophagy – “Autophagy has dual roles in cancer, acting as both a tumor suppressor by preventing the accumulation of damaged proteins and organelles and as a mechanism of cell survival that can promote the growth of established tumors. Tumor cells activate autophagy in response to cellular stress and/or increased metabolic demands related to rapid cell proliferation. Autophagy-related stress tolerance can enable cell survival by maintaining energy production that can lead to tumor growth and therapeutic resistance. As shown in preclinical models, inhibition of autophagy restored chemosensitivity and enhanced tumor cell death.” (Ref)
Bacteria, Parazites, etc. – Tumors (specifically thos ein the lungs) may be “populated” by bacteria and other parasites that just because of their mostly peripheral location may “absorb” the administrated (chemo) substance which as a result may not reach the tumor in high enough dose. There are various medicines that are both know to posed anti cancer properties and can at the same time address this issue:
- Pyrvinium pamoate
Fasting 2-3 days prior to chemo (or radiation) will also help: Fasting-like diet turns the immune system against cancer https://news.usc.edu/103972/fasting-like-diet-turns-the-immune-system-against-cancer/
See Also: this comment https://www.cancertreatmentsresearch.com/pyrvinium-pamoate/#comment-3065
Modulation of oxidative stress as an anticancer strategy (Ref.) http://www.nature.com/nrd/journal/v12/n12/full/nrd4002.html?message-global=remove
The regulation of oxidative stress is an important factor in both tumour development and responses to anticancer therapies. Many signalling pathways that are linked to tumorigenesis can also regulate the metabolism of reactive oxygen species (ROS) through direct or indirect mechanisms. High ROS levels are generally detrimental to cells, and the redox status of cancer cells usually differs from that of normal cells. Because of metabolic and signalling aberrations, cancer cells exhibit elevated ROS levels. The observation that this is balanced by an increased antioxidant capacity suggests that high ROS levels may constitute a barrier to tumorigenesis. However, ROS can also promote tumour formation by inducing DNA mutations and pro-oncogenic signalling pathways. These contradictory effects have important implications for potential anticancer strategies that aim to modulate levels of ROS. In this Review, we address the controversial role of ROS in tumour development and in responses to anticancer therapies, and elaborate on the idea that targeting the antioxidant capacity of tumour cells can have a positive therapeutic impact.
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