A radical approach to treating inoperable cancers that also cannot be irradiated

  1. Surely, even if the tumor is inoperable, one can still perform surgery and inject various tumor-specific poisons, and either collect the outflow from the tumors, purify it, and recycle it back into the body, or limit outflow from the tumors, and/or use poisons requiring high concentrations (so that the poisoning effect is greatly reduced when the poison comes back out with the tumor’s efferent blood supply, and diluted by the volume of the body.
  2. Chemotherapeutic agents that make sense are those that specifically attack the metabolic reprogramming that goes on within tumors containing cells exposed to a gradient of oxygen. Perhaps attacking pyruvate dehydrogenase A in the more hypoxic cells, which they need to regenerate NAD+ for their high level glycolysis, and perhaps attacking MCT-1 in the more oxygenated cells so that they take up less lactate and more of the glucose (which the diet will attempt to minimize) that the hypoxic cells need, and thus starve the more hypoxic cells for the already limiting glucose (compare J. Clin. Invest. 118:3835–3837. 2008).
  3. Stimulate and continue to periodically re-stimulate both the less specific innate immune system (e.g. by William Coley’s carefully controlled fever method) and the more specific adaptive immune system to kill cancers.
  4. Remove inhibitors and blockades to mitochondrial respiration (such as the removal of the phosphorylation-based inhibition of pyruvate dehydrogenase by 100 mg daily doses of thiamine) and jump start mitochondrial respiration to favor normal cells over tumor cells. High level restoration of mitochondrial respiration should kill off tumor cells with seriously defective mitochondrial respiration and possibly re-differentiate (extra vitamin D may help here) those tumor cells with functional but reduced respiration due to e.g. relative hypoxia, since under hypoxia, the hypoxia inducible factor induces both lactate dehydrogenase A (which increases the conversion of pyruvate to lactate) and activates pyruvate dehydrogenase kinase (which reduces the conversion of pyruvate to acetyl CoA and thus inhibits oxidative sugar metabolism).
  5. Tumors have cells experiencing a gradient of oxygenation (roughly paralleling the distance from the nearest blood vessel), with the more hypoxic ones being more resistant to radiation and chemotherapy. Oxygenation of the more hypoxic cells, reduction of HIF-1 expression, and mitochondrial respiration go hand in hand. Try to oxygenate tumors as much as possible. Take copious quantities of essential fats (thoroughly mixed into high protein food so that gastric lipase can more thoroughly digest them) to support this process and get plenty of aerobic exercise and some weight training. Do other things to exploit the Pasteur effect (oxygenation slows down fermentative growth) to slow the reproduction of cancer cells to below the total kill rate so that the tumors will eventually die off.
  6. Possible downside of essential fats, particularly if the ratio of omega 3: omega 6 exceeds about 1:2: weaken cytokine production and cytotoxicity of immune cells?
  7. Get regular injections of massive doses of sodium ascorbate.
  8. Take about a 0.5 to 1 gram of vitamin C an hour during waking hours to stimulate the immune system and to help prevent the shutdown of respiration due to too many free radicals. Other stimulants? Would like to try adding arginine to the essential amino acid cocktail to support NO bombardment of tumor cells, but if tumors turn out to be using arginine for reproduction, it could be problematic.
  9. Other supplements: plenty of antioxidants to inhibit the shut-down of fatty acid respiration from too many ROS that overwhelm the endogenous enzyme defenses. The low molecular weight antioxidant treatment may reduce the endogenous enzymes, but so be it, as long as the added antioxidants can prevent the slow down of fatty acid, ketone, glucose, and amino acid respiration. These supplements Include lipoic acid (biotin to combat possible lipoic acid-induced biotin deficiency), CoQ10, PQQ?, acetyl carnitine (supports long chain fat burning, and along with lipoic acid, CoQ10, and PQQ, strengthens mitochondria), beta alanine (to make a bit more carnosine, but not so much as to inhibit taurine transport).
  10. Two antioxidants deserve special mention because of another very specific function. N-acetyl cysteine (2 grams or more) and vitamin C (10 grams or more) to activate (maintain the ferrous state?) the PHD2 proline hydroxylase to hydroxylate HIF-1alpha and set it up to be turned over, following von Hippel Lindau and ubiquination. Probably wont work in von Hippel Lindau double mutants. Why turnover HIF-1alpha, if at all possible? To reduce the growth stimulus and angiogenic potential of VEGF and to reduce the expression of glycolytic enzymes, which are providing the energy for cell division. If glycolysis can be slowed down enough, the cells may die. If they do not die, they may replicate so slowly that the linear cell killing can triumph over the very slow exponential growth of the tumors, and eradicate them.
  11. N-acetyl cysteine and lipoic acid to boost glutathione levels in normal cells to reduce the rate of failure of reactivating mitochondrial respiration.
  12. Taurine to reduce the rate of free radical formation and to make more of the stronger bile acids to better absorb essential fats and fat soluble nutrients.
  13. The fasting and the low blood glucose also help by removing the inhibition on a key enzyme linking glutamine, which tumor cells take up avidly, and the TCA cycle, glutamate dehydrogenase. More alpha-ketoglutarate is made, which activates the TCA/OXPHOS and is used by the PHD2 to mark HIF-1alpha for destruction.
  14. An important bifurcation – I would try an alternative to antioxidant supplementation: No antioxidant supplementation. Let the endogenous defenses be induced to fight the free radicals. Since glucose is restricted, the body cannot run glucose fermentation, bypassing respiration, and thus the body cannot fail to still run respiration even when free radicals are plentiful.
  15. Further limit the reproductive rate of tumor cells by reducing the concentration of all of its principal carbon, nitrogen, phosphorus, sulfur, etc. sources. Use supplements of essential nutrients only – no real food because in this test protocol we must limit glutamine and alanine and all of the principal sulfur sources of tumors besides methionine, which is essential, as well as the most important carbon source, glucose. The ketogenic diet I suggested earlier -because it is high protein and high fat- will not limit glutamine and alanine – it may increase the level relative to a non-ketogenic diet. However, the body may need so much glutamine to function properly that any method of limiting glutamine may compromise health too much to be useful, and in any case this radical treatment is dangerous because if any of the conversions of the precursors of the non-essential amino acids into the non-essential amino acids is not occurring efficiently enough, there could be serious consequences. A treatment for cancer that accelerates death is an obvious loser.
  16. Consume the essential nutrients in a 3-5 hour window per day and fast for the remaining 19-21 to force respiration, to renew/rejuvenate cells by stimulating autophagy, to reduce and reverse insulin/IGF-1 growth signaling with glucagon dominance, and to put more pressure on those tumor cells that are less metabolically flexible and less metabolically adaptive than normal cells, and to slow down tumor growth during the long fast.
  17. Some other supplements needed: An unknown amount of the 8 essential amino acids. The essential amino acid requirements are in aggregate only about 13 grams, but 50 grams or so of total proteins is needed to repair muscles, an unknown number of grams are needed to maintain weight, and something is needed to make glucose, which is completely absent in the synthetic diet. First, we do not know how much glucose the body requires. Cells without mitochondria (such as RBCs) have a requirement for glucose but this is a small amout. Some people say the brain requires over 100 grams of glucose per day, but I think they err. Probably only about half of that is needed for the PPP, while the energy that the brain requires can be supplied – at least for a short time – by ketones. Now is it better to give the body non-amino acids to make glucose? Or is it better to give it more glucogenic essential amino acids at the risk of the liver making more glutamine and alanine that may end up supporting tumor reproduction? Is histidine actually essential to the cancer patient? Actually, what are the essential amino acids for cancer patients? is the more relevant question.
  18. A note on the PPP: it appears to supply the majority of NADPH for reductive biosynthesis and to serve as a ground zero antioxidant. But there are other ways to build up NADPH that may not involve so much glucose. For example, pyruvate -> oxaloacetate -> malate -> pyruvate. This cycle in essence exchanges NADH for NADPH. Could we risk lowering blood glucose more if we can get this cycle running efficiently and thereby slow down the reproductive rate of the tumor to below the kill rate of the combined forces killing tumor cells?
  19. Other supplements: All of the essential vitamins and minerals in their optimal forms, a group of fiber supplements for bulk, both essential fats and the fish oils. For calories: no sugar, no animal or plant proteins (too much additional glutamine and alanine!), just extra fat such as oleic acid, palmitic and stearic acids, which are good fuels. Easily burnable liquid purified MCT coconut oil also to relieve the respiratory strain and the strain on the carnitine transport system due to so much long chain fatty acid oxidation.
  20. A critical supplement: potent organic selenium compounds, known for cancer prevention more than cure.
  21. Copious lipases to make sure the fats are digested and absorbed. Fats and the ketones the liver will make from them are the lion’s share of the normal cells’ energy supply and by default must become the lion’s share of the energy supply of the tumor cells if they are to survive (we hope they do not).
  22. Some problems: nutrient deficiencies – both conditionally essential nutrients and no doubt there are essential nutrients we do not know about yet. The diet is clearly assuming -no doubt falsely, but how long can we do this? – that we can make everything else we need from these starting materials. We can suspend the fat-soluble nutrients in the essential fats/other fats mixture, but to what do we bind the essential fats to increase their initial solubility in water and their eventual digestion and absorption? Since we are adding amino acids, we could predigest the triglycerides as well prior to eating. Gosh, we’d be acting as fungi do in nature!
  23. Must nots: no acid blockers. We cannot afford poor absorption of the vitamins and minerals due to bacterial overgrowth of the small intestine.
  24. Will this radical approach also improve health (because of reduced total toxicity) in those without cancer? Will it kill cancer patients more quickly for lack of essential nutrients, especially the unknown conditionally essential nutrients? Could this be used intermittently in people without cancer to give the body a rest from food-based toxicity? Is an intermittent approach better for cancer therapy?
  25. Major caveats: Glutamine limitation seems self-defeating because critical illness seems to deplete glutamine pools, because glutamine is so central in amino acid metabolism, is used by the kidneys to supply the ammonia to counterbalance strong acid excretion, is key for the health of the intestinal and immune system, and even as the major precursor to glutathione via glutaminase, as well as a key inhibitor of cachexia. Tumors weaken the immune system in many ways, but two methods relate directly to glutamine: tumors consume glutamine avidly, thus depleting it for the immune system and the rest of the body, weakening it in the process, and tumors excrete glutamate, from glutaminase activity on glutamine, and this glutamate directly weakens the immune system.
  26. The key question: in critical illness is glutamine net beneficial to the health of the body? For example, in cancer, does glutamine help the body cope with cancer more than it helps the cancer overcome the body’s defenses? If the answer is yes, forget glutamine limitation. Instead I would try these other things within the context of a food-based high protein, moderately high fat, low carbohydrate diet.
  27. In addition to using glutamine as a nitrogen source and as a fuel, it seems like the cancer weakens the immune system, particularly macrophages, by using glutamine to make and excrete two types of compounds, glutamate (as noted above) and free fatty acids. Yet we can counter that immune system weakening by strengthening the immune system in a lot of different ways, including massive regular (repeated hourly) doses of vitamin C and some supplemental arginine for NO production.
  28. A wild thought: what if we add an appropriate amount of glutamate dehydrogenase to the blood stream to convert the excess glutamate to alpha-keto-glutarate? Would turn a compound that helps tumors, glutamate, by hurting the immune system, into a compound, alphaketoglutarate, that more than likely hurts hypoxic cells in tumors by supporting mitochondrial respiration. Probably won’t work and could promote methemoglobinemia. Oxoglutarate is too highly oxidized. We need to kill the cells that are excreting all of the compounds like glutamate and free fatty acids that are weakening the immune system that we are trying to activate to kill the cells that are weakening it.
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