57-68: Implementation of Cocktail Therapy for Cancer

Here is a summary chart I prepared to comprehensively summarize the various categories of conventional and unconventional approaches to cancer.  This should cover most known anti-cancer treatments, conventional or unconventional, alternative or otherwise, out there.  I draw this in the office for my patients frequently so that they can see what they are doing, what else is there, and what else they could they may doing, and it seems helpful. I had originally wanted to include this in the book but the publisher thought that it could further confuse some readers, but I present here anyway as some may find it helpful.

Conventional and Unconventional approaches to Cancer

Notes
1) Chemotherapy’s usual mechanism of action at full dose is meant to be cytotoxic, i.e. to kill the cancer cells directly, but when deployed at 10-20% of its full dose or at a so-called “metronomic” dose, its main mode of action seems to be anti-angiogenic + immunomodular and has much less side-effects.

2)”Targeted” therapy is a catch-all term and doesn’t refer to a drug’s biological mode of action, thus it could be cytotoxic, antiangiogenic, apoptotic or epigenetic or immune all depending on what specific target it is referring to.  Although a modern concept, classical drugs such as Tamoxifen is a typical targeted therapy since it targets the estrogen receptor.

3) Some herbs are cytotoxic, and indeed quite a few chemotherapies (e.g. taxol) are derived from plants.

4) The main anti-cancer potential from vitamins are from the fat soluble vitamins A, D, E, and K and the mechanism is largely apoptotic.

5) The main biological mechanism of diet and lifestyle mechanism is via epigenetics and sex and growth or stress hormonal modulation, and they affect immune function as well.

6) Mental and spiritual well being seem to mainly enhance the immune system (so-called psychoneuroimmunological system) and balance the (stress and sex) hormonal systems, which are closely related.

7) There should probably be an “Other” category under biology, as there are other anti-cancer mechanisms such as autophagy or even yet unknown processes or mechanisms.  We should not forget that epigenetics is a relatively new science and antiangiogenesis as an anticancer mechanism is discovered not so many decades ago.

p. 63-66 Importance of dietary factors This section could be greatly expanded and as we doctors focus more on pharmaceuticals, many patients are most interested in what best to eat to prevent and to treat cancer.  This subject can surely be another title for a sequel to “Beyond the Magic Bullet” ! It could perhaps be said that cancer is a modern scourge, especially as medicine is curing more and more ailments, we seem to be left with cancer as the one of the last obstacles to true longevity.  How is it that cancer seems more prevalent now than ever?  And what has this to do with diet?  Well, there seems to be a strong link between eating “well” (not necessarily eating healthy) and eating too much in well-fed modern societies, and cancer.  Cancer has certainly not been causally associated with famine and malnutrition ! But is there any evidence?  And what has over-eating to do with cancer?  For example, we know as a epidemiologic fact that overweight women are more likely to develop breast cancer as well as are more likely to die of the cancer.  A recent review of 43 studies examining obesity and breast cancer outcome found a 33% higher risk for breast cancer death when comparing obese with lean women (Protani et al. Breast Cancer Res Treat 123:627,’10).  A related research examining 18,762 breast cancer patients found that metastases and deaths were respectively 46% and 38%  more likely for those with a BMI > 30 kg/m2 compared with those whose BMI were under 25 kg/m2 (Ewertz et al. J Clin Oncol 29:25,’10). The next question is whether shedding some pounds may improve survival in obese breast cancer patients, and the WINS study found that a 6lb weight loss correlated with a significant reduction cancer recurrences and a trend towards improved mortality (Chlebowksi et al. San Antonio Breast Cancer Symposium Dec 2006).  Increasingly, evidence is converging to point to the important contribution of too much far and calorie intake to cancer incidence and mortality, but what are some of the possible biological mechanisms? There could be many. In 2010, Kevin Gardner et al at the NCI found that the processing of calories affects the activity of a gene (BRCA1) that controls a tumor suppressing protein (See here) which is significant because this is one of  the first molecular link of caloric intake and cancer. What Dr. Gardner found is that the more calorie rich molecules the body processes (i.e. the more carbs one eats) the more the cancer risk via a genetic mechanism in susceptible individuals. What is the take home message:  Diet ! Lose weight ! Reduce carbs and fat !

Related to the above is a diet that deserves extra mention, the ketogenic diet. This is eloquently expounded in Prof. Seyfried’s marvelous text “Cancer as a Metabolic Disease”. The simplistic overview of the diet is to use low carbs PLUS high fats in order to induce a ketogenic state where ketones are utilized by normal cells (cancer cells cannot utilize ketones a fuel and thus die) instead of glucose.  It is not easy to carry out, but whats important about this diet is that there is clinical evidence of its efficacy, especially for brain tumors, where published citations of reversals and remissions of patients utilizing this approach have been reported. Anyone interested in this approach must read Prof. Seyfried’s book.

Cocktailing the diet with agents such as off-label agents such as metformin and unapproved agents such as DCA (dichloroacetic acid) may represent a more comprehensive metabolic approach to the treatment of cancer.

p. 66-67 I maybe remiss in not putting in a section on exercise or lifestyle in the non-conventional section (p.59-67), and it is by no means not important, especially for preventing cancer. Specifically regarding exercise, moderate activity has been associated with up to a 50% reduction in recurrence and mortality in colon cancer (Meyerhardt JA, et al. J Clin Oncol 24:3535-3541,2006). Looking from a different angle, many Americans have an unhealthy lifestyle ( up to 70% overweight, 50% with diets < 5 daily servings of fruits/veggies, 16% with moderate to heavy alcohol consumption, and 70% with sedentary lifestyles) all factors of which increase their risk of cancer, thus lifestyle modification should be integral in any cancer preventative program, primary or secondary.

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  1. July 1, 2013 at 7:36 pm

    Glucose is commonly metabolized via glycolysis in cancer cells. Typically, hexokinase II is bound to the VDAC pore on the mitochondria to provide unlimited access to mitochondrial ATP. Also, many cancer cells can metabolize glutamine through glutaminolysis. Much of the glutamine is conjectured to made available through tumor-stroma crosstalk that induces autophagy in near-tumor stroma to produce needed amino acids for cell construction. Therefore, ATP from glycolysis and/or glutaminolysis and amino acids from the neighboring support group of cooperative stroma. Bodywide signaling mobilizes glutamine from host muscle hence the cachexia observed in the host. A very nasty disease. Quite evolutionary, though. I think the key is the metabolism. Maybe mitochondrial DNA deletions/additions leading to an evolutionary survivability advantage leading to nuclear aneuploidy of mobilized adult or bone-marrow derived stem cells. These aneuploid guys aren’t really human, just human-like enough to fool/highjack immune system.

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