Cancer is a disease that continues to baffle even the most advanced research institutes. Exhaustive studies continue to be conducted in a desperate attempt to understand the disease and how we may effectively prevent and treat it.
This article aims to provide you with a better understanding of the biological processes known to contribute to the growth and metastases of cancerous tumours; and outlines some of the complementary medicines that appear to demonstrate benefits in stunting tumour growth, reducing the risk of metastases and assisting the body in fighting the disease. By no means do we claim to have all the answers, nevertheless armed with this knowledge your patient outcomes may be improved.
UNDERSTANDING TUMOUR GROWTH AND METASTASES
There are a multitude of factors that may lead to the development of a malignant tumour and cancer. Numerous lifestyle factors, hormonal and genetic influences, inflammation, cellular and/or DNA damage can all play a role in the initiation of tumour growth. However it is most often the metastases or “spreading” of the cancer that will result in the illness becoming life threatening.
To identify how to best prevent the growth and metastases of a cancerous tumour it is first important to understand how the process occurs.
Apoptosis refers to the process of programmed cell death. Telomeres on the end of chromosomes within a cell’s nucleus “shorten” with each cell division. Once a chromosome has divided a specific number of times the telomere becomes fully eroded and the chromosome is damaged initiating cell death or “apoptosis”. The opposite process to telomere shortening is carried out by an enzyme known as “telomerase”. Telomerase maintains the length of telomeres and is responsible for a cell’s immortality. Most cells in the body have little telomerase activity, however a high level of activity has been identified in embryonic stem cells and the vast majority of tumour cells. It is believed that mutations to DNA result in defective apoptosis. Potential overactivity of telomerase results in rapid cell division where immortal cells may clump together and form a tumour.[1-3]
Due to these findings, intense research has investigated control of apoptosis as a potential target for cancer treatment. Research focuses include DNA mutations, telomerase activity and endogenous signals believed to contribute to anti-apoptotic activity.[1-3]
Angiogenesis is the process of formation of new blood vessels from pre-existing vessels or endothelial cell precursors. It is essential in foetal growth, inflammation, wound healing, tumour growth and metastases.
Research has identified that once a tumour reaches 1-2mm in diameter it will not continue to increase in size without angiogenesis. A greater network of blood vessels is required to provide the nutrients, oxygen and waste removal essential for growth.
Numerous signalling agents are involved in angiogenesis. The tumour releases molecular signals to the surrounding tissue, activating specific genes that ultimately result in the synthesis of proteins to encourage the growth of new blood vessels, e.g. activator molecules that prompt the growth and division of vascular endothelial cells.
Metastases is the spread of cancer from one part of the body to another. Carcinoma cells may break away from a primary tumour and invade surrounding tissue or enter the lymphatic or circulatory systems. It is via these systems the cells may reach other organs, clump together and form a metastatic tumour.
POTENTIAL TARGETS FOR THERAPY
Research has discovered numerous naturally occurring signalling molecules that contribute to the activation of angiogenesis and potentially drive metastasis.
Inflammatory mediators including nuclear factor kappaB (NFkB) and pro-inflammatory cytokines (IL-8, TNF-alpha) are involved in cancer progression. Cytokines elicit a host of responses in tumour cells resulting in proliferation, differentiation and tumorigenesis - suggesting that anti-inflammatory compounds may be of benefit.
Vascular endothelial factor (VEGF) and basic fibroblast growth factor (bFGF) are two pro-angiogenesis proteins that appear to be the most important for tumour growth. As a result numerous trials have been conducted to identify the most effective mechanisms for inhibiting VEGF and bFGF driven angiogenesis, so to stunt tumour growth and reduce the risk of metastasis.
Galactin-3 (Gal-3) has been identified as a significant factor in the clumping together of cancer cells, implicating it in metastases and tumorigenicity, associations to the inhibition of apoptosis, cancer progression and inflammation. Inhibition of Gal-3 binding in in vitro and in vivo studies have shown promise in reducing the development of metastatic tumours.
AMP-Activated Protein Kinase (AMPK) is an energy sensor in all cells which is often activated through exercise, when depleted ATP levels are detected. It inactivates a number of metabolic enzymes involved in ATP-consuming cellular events. AMPK activity is deficient in the presence of systemic inflammation and in tumour cells . Published studies indicate that activation of AMPK strongly suppresses cell proliferation in tumour cells through reductions in the availability of energy substrates and regulation of the cell cycle.[6,7]
Numerous natural compounds have demonstrated the ability to mimic the metabolic benefits of exercise and activate AMPK and these are covered in Table 1. Managing inflammation will also ensure AMPK activation is not suppressed.
CONSIDERATIONS FOR COMPLEMENTARY CANCER TREATMENTS
Prevention is better than cure and overall health is of course key in any disease management program. Lifestyle factors including the avoidance of known carcinogens, stress management and a healthy diet rich in plant foods and beneficial fats are the first step towards being cancer-free.
Table 1. provides a comprehensive breakdown of some of the natural compounds which have demonstrated effectiveness against specific aspects of cancer development. A combination of such supplements may prevent tumour development, stunt tumour growth, prevent metastases and support the cancer patient after surgery and during chemo or radiation therapy.
Nutritional Support for the Cancer patient
A number of nutritional interventions may be of benefit to the cancer patient receiving orthodox treatments of radiation and chemotherapy.
Severe complications related to these therapies (and to the presence of cancer itself) include cachexia and immune suppression.
The development of cachexia refers to significant loss of body weight and muscle atrophy. It may stem from anorexia, nausea, reduced digestive health and/or excessive cytokine release.
If not addressed cachexia may be life threatening. In certain advanced cancers (e.g. pancreatic cancer), cachexia and malnutrition, not the cancer itself, are the primary factors in mortality, indicated in up to 80% of deaths.
Many studies have identified excessive pro-inflammatory cytokine release as a key factor in cachexia development, combined with the high energy consumption of numerous metastatic tumours.[33-35] Cytokines have many systemic outcomes, they initiate inflammatory pathways, up-regulate of hypothalamic-pituitary-adrenal (HPA) axis activity and stimulate the melanocortin system leading to increases in metabolic rate and anorexia. The result is significant increases in energy output. Glycogen and lipid stores are rapidly exhausted, leading to muscle atrophy and severe fatigue.
EPA and DHA
A diet rich in energy and nutrition, with sufficient protein is vital to address muscle atrophy, weight loss and fatigue. Management of the inflamed state will also benefit from adequate nutrient intake. Anti-inflammatory compounds, including EPA and DHA have shown promising results in cachexia management. Significant improvements in overall weight and lean body mass, increased anti-inflammatory eicosanoid synthesis and reductions in inflammatory markers (e.g. CRP, TNF-alpha, IL-6) have been demonstrated.[33,35]
GIT Health and Hydration
If cachexia and/or anorexia is present it is essential to ensure that GIT integrity and digestive function is maintained. Increased GIT permeability may prevent optimal nutrient absorption and allow passage of pathogens that may cause infection or exacerbate systemic inflammation. During periods of stress intracellular levels of glutamine drop as it is used by gluconeogenesis in muscles and in glutathione synthesis. Supplementing glutamine may be of benefit during this time as it plays a key role in metabolism, structure and function of the entire gastrointestinal tract and its extensive immune system. Glutamine may prevent gut mucosal atrophy and will prevent increases in intestinal permeability. N-acetyl-glucosamine also supports GIT health via its role in maintenance and repair of mucous membranes.
Significant fluid can occur if severe nausea, vomiting or diarrhoea has developed. Good hydration is vital to prevent electrolyte imbalances that may contribute to muscle cramps and spasms, irregular heart beat, and will allow effective elimination of toxic metabolites from the body.
As we improve our understanding of cancer development and progression we are able to identify further options for treatment and disease management. There are numerous compounds existing in nature that have demonstrated benefits in addressing a range of cancer types, and many of these may complement orthodox approaches by preventing the undesirable side effects and reducing risk of metastases development in the future.
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