Dr. Weeks’ Comment: “If you can get people to ask the wrong question, then the answer doesn’t matter.” (Thomas Pychon – Gravity’ Rainbow) “Which oncogenes are sensitive to which chemotherapy agents?” is the wrong question since the cancer process (metabolic disorders) creates the genetic aberrations; the oncogenes do NOT create the cancer.
Trying to create a protocol to address oncogenes is treating the symptom as I discussed at length in this lecture given at the Truth about Cancer live symposium in Orlando 2017. Professor Thomas Seyfried champions this position most articulately in the following 2014 article. But when you try and dissuade your oncologist from preforming the standard of care (testing for oncogenes) remember that testing for and treating oncogenes is BIG BUSINESS, so reason alone does not seem to persuade.
“… Tailored therapies, unique to the genomic defects within individual tumors, are viewed as the future of cancer therapeutics ( 2 , 24 ). This therapeutic strategy would certainly be logical if the nuclear somatic mutations detected in tumors were the drivers of the disease. How certain are we that tumors arise from somatic mutations and that some of these mutations drive the disease? It would therefore be important to revisit the origin of the gene theory of cancer…”
“…Advanced metastatic cancers can become manageable when their access to fermentable fuels becomes restricted…”
Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation. The genomic instability observed in tumor cells and all other recognized hallmarks of cancer are considered downstream epiphenomena of the initial disturbance of cellular energy metabolism. The disturbances in tumor cell energy metabolism can be linked to abnormalities in the structure and function of the mitochondria. When viewed as a mitochondrial metabolic disease, the evolutionary theory of Lamarck can better explain cancer progression than can the evolutionary theory of Darwin. Cancer growth and progression can be managed following a whole body transition from fermentable metabolites, primarily glucose and glutamine, to respiratory metabolites, primarily ketone bodies. As each individual is a unique metabolic entity, personalization of metabolic therapy as a broad-based cancer treatment strategy will require fine-tuning to match the therapy to an individual’s unique physiology.
Cancer is a disease involving multiple time- and space-dependent changes in the health status of cells and tissues that ultimately lead to malignant tumors. Neoplasia (abnormal cell growth) is the biological endpoint of the disease. Tumor cell invasion into surrounding tissues and their spread (metastasis) to distant organs is the primary cause of morbidity and mortality of most cancer patients ( 1-5 ). A major impediment in the effort to control cancer has been due in large part to the confusion surrounding the origin of the disease. Contradictions and paradoxes continue to plague the field ( 6-10 ). Much of the confusion surrounding cancer origin arises from the absence of a unifying theory that can integrate the many diverse observations on the nature of the disease. Without a clear understanding of how cancer arises, it becomes difficult to formulate a successful strategy for effective long-term management and prevention. The failure to clearly define the origin of cancer is responsible in large part for the failure to significantly reduce the death rate from the disease ( 2 ). Although cancer metabolism is receiving increased attention, cancer is generally considered a genetic disease ( 10 , 11 ). This general view is now under serious reevaluation ( 2 , 12 ). The information in this review comes in part from our previous articles and treatise on the subject ( 2 , 13-17 ).
Provocative question: does cancer arise from somatic mutations?
Most of those who conduct academic research on cancer would consider it a type of somatic genetic disease where damage to a cell’s nuclear DNA underlies the transformation of a normal cell into a potentially lethal cancer cell ( 7 , 10 , 11 , 18 ). Abnormalities in dominantly expressed oncogenes and in recessively expressed tumor suppressor genes have been the dogma driving the field for several decades ( 7 , 10 ). The discovery of millions of gene changes in different cancers has led to the perception that cancer is not a single disease, but is a collection of many different diseases ( 6 , 11 , 19 , 20 ). Consideration of cancer as a ”˜disease complex’ rather than as a single disease has contributed to the notion that management of the various forms of the disease will require individual or ”˜personalized’ drug therapies ( 2 , 21-23 ). Tailored therapies, unique to the genomic defects within individual tumors, are viewed as the future of cancer therapeutics ( 2 , 24 ). This therapeutic strategy would certainly be logical if the nuclear somatic mutations detected in tumors were the drivers of the disease. How certain are we that tumors arise from somatic mutations and that some of these mutations drive the disease? It would therefore be important to revisit the origin of the gene theory of cancer.
The gene theory of cancer originated with Theodor Boveri’s suggestion in 1914 that cancer could arise from defects in the segregation of chromosomes during cell division ( 18 , 25-29 ). As chromosomal instability in the form of aneuploidy (extra chromosomes, missing chromosomes or broken chromosomes) is present in many tumor tissues ( 21 , 30-32 ), it was logical to extend these observations to somatic mutations within individual genes including oncogenes and tumor suppressor genes ( 18 , 33-36 ). Boveri’s hypothesis on the role of chromosomes in the origin of malignancy was based primarily on his observations of chromosome behavior in nematodes ( Ascaris ) and sea urchins ( Paracentrotus ) and from his consideration of von Hansemann’s earlier observations of abnormal chromosome behavior in tumors ( 18 , 25 , 29 ). In contrast to Boveri’s view of aneuploidy as the origin of cancer, von Hansemann considered the abnormal chromosome behavior in tumors as an effect rather than as a cause of the disease ( 25 ). Although Boveri’s hypothesis emerged as the foundation for the somatic mutation theory of cancer, it appears that he never directly experimented on the disease ( 18 , 25 , 29 ). The reason for the near universal acceptance of Boveri’s hypothesis for the origin of cancer is not clear but might have been linked to his monumental achievement in showing that Gregor Mendel’s abstract heredity factors resided on chromosomes ( 29 ). Boveri’s cancer theory was also consistent with the gradual accumulation of evidence showing that DNA abnormalities are abundant in cancer cells.
In his 2002 review, Knudson stated that, ”˜considerable evidence has been amassed in support of Boveri’s early hypothesis that cancer is a somatic genetic disease’ ( 37 ). The seeds of the somatic mutation theory of cancer might have been sowed even before the work of von Hansemann and Boveri. Virchow considered that cancer cells arose from other cancer cells ( 38 ). Robert Wagner provided a good overview of those early studies leading to the idea that somatic mutations give rise to cancer ( 38 ). It gradually became clear that almost every kind of genomic defect could be found in tumor cells whether or not the mutations were connected to carcinogenesis ( 10 , 11 , 18 , 26 , 31 ). The current somatic mutation theory involves a genomic landscape of incomprehensible complexity that also includes mysterious genomic ”˜Dark Matter’ ( 2 , 10 , 11 , 19 ). Although massive evidence exists showing that genomic instability is present to some degree in all tumor cells, it is unclear how this phenotype relates to the origin of the disease. It appears that almost every neoplastic cell within a naturally arising human tumor is heterogeneous in containing a unique genetic architecture ( 31).
TOWARDS THE END OF THE ARTICLE….
The novelty of the metabolic approach to cancer management involves the implementation of a synergistic combination of nutritional ketosis, cancer metabolic drugs and HBO 2 T. This therapeutic approach would be similar to the ”˜Press-Pulse’ scenario for the mass extinction of organisms in ecological communities ( 223 , 224 ). The KD-R would act as a sustained ”˜Press’, whereas HBO 2 T and metabolic drugs would act as a ”˜Pulse’ for the mass elimination of tumor cells in the body. Some of the cancer metabolic drugs could include 2-deoxyglucose, 3-bromopyruvate and dichloroacetate ( 56 , 120 , 225-227 ). This therapeutic strategy produces a shift in metabolic physiology that will not only kill tumor cells but also enhance the general health and metabolic efficiency of normal cells, and consequently the whole body ( 189, 209 ). We view this therapeutic approach as a type of ”˜mitochondrial enhancement therapy’ ( 192 ). As we consider OxPhos insufficiency with compensatory fermentation as the origin of cancer, enhanced OxPhos efficiency would be anti-carcinogenic.
Many cancers are infected with human cytomegalovirus, which acts as an oncomodulator of tumor progression ( 228 ). Products of the virus can damage mitochondria in the infected tumor cells, thus contributing to a further dependence on glucose and glutamine for energy metabolism ( 18 , 229-231 ). The virus often infects cells of monocyte/macrophage origin, which are considered the origin of many metastatic cancers ( 145 , 146 , 232 , 233 ). We predict that the KD-R used together with anti-viral therapy will also be an effective Press-Pulse strategy for reducing progression of those cancers infected with human cytomegalovirus ( 234 ).
Advanced metastatic cancers can become manageable when their access to fermentable fuels becomes restricted. The metabolic shift associated with the KD-R involves ”˜keto-adaptation’. However, the adaptation to this new metabolic state can be challenging for some people. The administration of ketone esters could conceivably enable patients to circumvent the dietary restriction generally required for sustained nutritional ketosis. Ketone ester-induced ketosis would make sustained hypoglycemia more tolerable and thus assist in metabolic management of cancer ( 235 , 236 ). As each person is a unique metabolic entity, personalization of metabolic therapy as a broad-based cancer treatment strategy will require fine-tuning based on an understanding of individual human physiology. Also, personalized molecular therapies developed through the genome projects could be useful in targeting and killing those tumor cells that might survive the non-toxic whole body metabolic therapy. The number of molecular targets should be less in a few survivor cells of a small tumor than in a heterogeneous cell population of a large tumor. We would therefore consider personalized molecular therapy as a final strategy rather than as an initial strategy for cancer management. Non-toxic metabolic therapy should become the future of cancer treatment if the goal is to manage the disease without harming the patient. Although it will be important for researchers to elucidate the mechanistic minutia responsible for the therapeutic benefits, this should not impede an immediate application of this therapeutic strategy for cancer management or prevention.
read the entire article HERE
Further information: watch this YOUTUBE esp at min 44:00 “…In the oncology field they don’t have any idea about it. They don’t even know about it. They dn’t understand the concepts. They are all locked into finding some gene based therapy that doesn’t work and that’s the unfortunate situation we are in today.”
HERE is the NEJM article presenting the rationale for focusing on oncogenes: This is the standard of care and the conventional approach. Now that you have read the minority opinion by Prof. Seyfried, read the majority opinion with the astute minority criticisms in mind.