Aristotle said it first, the whole is greater than the sum of the parts. Christian Smutz brought the holism concept to the modern era with his book Holism and Revolution. This background was highlighted in greater detail in my previous post on Holistic cancer. The general concept is that the whole transcends the individual parts. Holistic medicine is a non-compartmentalized approach to healthcare. With less information, the ancients got it more right than the experts of today with significantly more information.
A holistic approach to cancer is no different. The holistic approach transcends all levels. A holistic approach to cancer is found in causation, testing, treatment, and in maintenance therapy. It is holistic in the whole sense of the word. This post will look at a holistic approach to some of the causes of cancer.
A holistic approach to the causes of cancer include:
- Lifestyle
- Epigenetics
- Hypoxia
- Inflammation
- Mitochondria
- Metabolic dysfunction
- Voltage
- Acid/Base balance
- Redox
- Tumor Microenvironment (TME)
- Immune dysfunction
- Hormones
- Toxicants and detoxification dysfunction
- Infection
- The Gut
- other associated deficiencies
There are and can be many more contributors, but this post is going to be long enough. To condense the quantity of information in this post, I will break up into a series of posts. I want to highlight each point in detail individually.
Lifestyle
Conventional medicine continues to push denial on the connection between lifestyle, particularly diet and cancer. The science is precise on the matter. In contrast to the opinion often espoused by physicians, including conventional Oncologists, we are products of our collective environment, and it is our lifestyle choices that dictate much of our environment. No matter the denial, the evidence points to the contrary. What we put in our mouth effects cancer risk and cancer healing.
Our nutrition choices, or lack there of, can benefit the whole of the body or damage the whole of the body. Lifestyle can include diet, stress, sleep/wake cycles, relationships, exercise/activity level, weight, home, and many others. A recently published article highlighted the connection between diet and cancer [1]. In this study model, dietary choices increase the toxicity of chemotherapy up to 100 fold. The mechanism, by researchers at the University of Virginia, was found to be through the dietary alterations in the gut microbiome. I have often said that diet is love language, or not, with our DNA. This study shows that diet is the means to alter the gut microbiome to increase or possibly decrease chemotherapy toxicity. In essence, the lifestyle choice of what we put in our mouth lays the groundwork for toxicity from chemotherapy. So much for the idea that nutrition plays no role in cancer treatment. In fact, If doctors are telling patients with cancer to eat whatever they want, i.e. hamburgers, steak, sugar… they are in effect increasing the toxicity and morbidity of treatment in patients. Their is an important phrase that should be on the tongue of every physician—“first do no harm”.This study just focused on diet. This point doesn’t take into account all the other individual lifestyle choices, that don’t exist in a bubble, and their collective combination.
Epigenetics
Epigenetics is an exciting new science that is making tremendous progress and promise in the treatment of dis-eases like cancer. Epigenetics means “above genetics”. The epigenome is the total number of modifications of the DNA (genome) in response to the environment (i.e., diet, stress…). This is the body’s attempt to regulate the activity and expression of all the genes (epigenetics) within the genome in response to its environment. While DNA is the different pieces of the puzzle that is the body, epigenetics is the directions for how those genes, the “pieces,” are used in response to the environment. This process of adaptation occurs throughout life. These adaptations are inheritable. These adaptations can be passed from generation to generation for generations. This inheritable epigenetic modifications is called Transgenerational Inheritance [2]. Epigenetic alterations can and will occur at any time, including conception, pregnancy, puberty, stress, and beyond. These are normal processes that take place throughout this existence we call life and control how a body changes and adapts to its environment. In addition to these normal processes, it is apparent that environmental factors and life events can affect each individual’s epigenome as well, which means you have a significant amount of control over your health now and your health potential in the future. Epigenetics brings each individual’s healing potential within their grasp.
Scientists are evaluating and testing new therapies that will use the epigenome to fight cancer. Just look at chemotherapy alone. Maximum tolerated chemotherapy is associated with significant, serious side effects. Instead of using high doses of toxic chemotherapy to attack the cancer cells, patients in trials are receiving lower doses of medication as a result of epigenomic targeting, explicitly directed towards the cancer cells while bypassing healthy cells [3]. These patients are showing positive results and are suffering from fewer side effects from the treatments. Now there is a novel concept, target the cancer and not the patient.
Hypoxia
Oxygen is essential to life on earth. Hypoxia is the lack of oxygen. Without oxygen, life in its current form would not exist. Hypoxia is present at the genesis of cancer—called carcinogenesis. As critical as oxygen is to life, the absence of oxygen is equally essential to the development of cancer. The whole body cannot be hypoxic, which equals no life. Instead, hypoxia is critical in the Tumor Microenvironment (TME). Hypoxia in the TME alters energy production via the Warburg effect. Hypoxia increases lactate production to increase the acidic environment that is so characteristic of the cancer TME. Hypoxia alters the immune system in the TME to protect and preserve the growing tumor from the immune system. All at the expense of the body. Beyond the driving force that is hypoxia in the genesis of cancer, hypoxia is the push to spread cancer. Hypoxia drives the production of blood vessel growth (angiogenesis) that is so critical to the physical cell escape in metastasis. Hypoxia is also essential in how cancer can escape the immune system, both locally and systemically, in metastasis.
Inflammation
Inflammation is the bed that cancer lies in. Inflammation is not de-facto the enemy of the body. That is an over-simplified view. Inflammation is in fact a critical, necessary component of the healing process. Just look at a paper cut. Immediately, the site is painful, red, swollen, and hot. These are the cardinal signs and symptoms of inflammation that prevent secondary infection and initiate the healing process. However, in the described setting of the paper cut, the inflammation subsides once the threat of secondary infection is gone and the healing process is in full motion. In cancer, inflammation does not turn off, but in fact, turns on the body. In many ways, cancer uses the immune system and inflammation signaling to co-opt the immune system against the body.
Cancer requires chronic inflammation, yet cancer stimulates the production of inflammation. Inflammation is a by-product of immune system signaling. Immune system signaling and inflammation can inhibit cancer initiation, growth, and spread. Likewise, Immune signaling and inflammation can promote cancer initiation, growth, and spread. In many ways, NF-kappaB sits at this crossroad of inflammation and cancer [4]. NF-kappaB is a key genetic transcription factor that stimulates inflammation in cancer to promote tumorigenesis [5]. Disordered immune function and Inflammation are present in the Tumor Microenviroment (TME) [6]. The inflammatory TME promotes NF-kappaB activation. It is the activation of NF-kappaB that further stimulates the production of inflammatory signals, called cytokines, that further increase pro-carcinogenic inflammation and even immune suppression. The result is dysfunction of the immune system, evasion of the immune system, and even suppression of the immune system, which leads to growth [7], survival [8], invasion and metastasis of cancer [9].
Inflammation is the bed that cancer lies in. Inflammation is not de-facto the enemy of the body and is an over-simplified view of inflammation. Inflammation is, in fact, a critical, necessary component of the healing process. Just look at a paper cut. Immediately, the site is painful, red, swollen, and hot. These are the cardinal signs and symptoms of inflammation that prevent secondary infection and initiate the healing process. However, in the described setting of the paper cut, the inflammation subsides once the threat of secondary infection is gone, and the healing process is in full motion. In cancer, inflammation does not turn off, but in fact, turns on the body. In many ways, cancer uses the immune system and inflammation signaling to co-opt the immune system against the body.
Cancer requires chronic inflammation, yet cancer stimulates the production of inflammation. Inflammation is a by-product of immune system signaling. Immune system signaling and inflammation can inhibit cancer initiation, growth, and spread. Likewise, Immune signaling and inflammation can promote cancer initiation, growth, and spread. In many ways, NF-kappaB sits at this crossroads of inflammation and cancer . NF-kappaB is a critical genetic transcription factor that stimulates inflammation in cancer to promote tumorigenesis . Disordered immune function and inflammation are present in the Tumor Microenvironment (TME) . Inflammatory TME promotes NF-kappaB activation. It is the activation of NF-kappaB that further stimulates the production of inflammatory signals, called cytokines that also increase pro-carcinogenic inflammation and even immune suppression. The result is the dysfunction of the immune system, evasion of the immune system, and even suppression of the immune system, which leads to growth , survival , invasion, and metastasis of cancer .
Look for the remaining articles of this series on the holistic causes of cancer to post in the coming weeks.
[1] Ke W, Saba JA, Yao C et al. Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion. Nat Commun 11, 2587 (2020). https://doi.org/10.1038/s41467-020-16220-w
[2] Bošković A, Rando OJ. Transgenerational Epigenetic Inheritance. Annual Review of Genetics. Nov 2018;52:21-41. https://doi.org/10.1146/annurev-genet-120417-031404
[3] Chan TS, Hsu CC, Pai VC, et al. Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells. J Exp Med. 2016;213(13):2967-2988. doi:10.1084/jem.20151665
[4] Karin M. NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol. 2009;1(5):a000141. doi:10.1101/cshperspect.a000141
[5] Hagemann T, Lawrence T, McNeish I, Charles KA, Kulbe H, Thompson RG, Robinson SC, Balkwill FR. “Re-educating” tumor-associated macrophages by targeting NF-kappaB. J Exp Med. 2008;205:1261–1268. doi: 10.1084/jem.20080108.
[6] Mantovani A. Molecular pathways linking inflammation and cancer. Curr Mol Med. 2010;10:369–373. doi: 10.2174/156652410791316968.
[7] Joyce D, Albanese C, Steer J, Fu M, Bouzahzah B, Pestell RG 2001. NF-κB and cell-cycle regulation: The cyclin connection. Cytokine Growth Factor Rev 12:73–90
[8] Liu ZG, Hsu H, Goeddel DV, Karin M 1996. Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-κB activation prevents cell death. Cell 87:565–576
[9] Huang S, Pettaway CA, Uehara H, Bucana CD, Fidler IJ 2001. Blockade of NF-κB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis. Oncogene 20:4188–4197
