How to Stop Metastasized Terminal Colon Cancer, Part1

May 29, 2010, Featured in Cancer and Natural Medicines, 0 Comments

Colon cancer claims 200,000 lives in Europe and the USA each year. With 300,000 new cases per year, it is the second commonest cancer and is therefore highly relevant to general medical practice. Surgical treatment is still a viable option in order to extend the patient’s life. Doctors can remove the section of the colon with the tumor and sew the healthier sections together. Freezing the tumor and removing it, also known as cryotherapy, is also a viable option. Surgery may also be an option to remove other infected body parts, depending on the size of the areas infected.


However, in most patients, there is no evidence of distant metastasis at the time of surgery, but the cancer has penetrated deeply into the colon wall or reached adjacent lymph nodes. These patients are at risk of tumor recurrence either locally or in distant organs such as liver and lungs. Once cancer is no longer local to one organ, it can reside microsopically in many places. Surgery has its cost – it forces the immune system to divert its attention to healing the wounds. Meanwhile, the microscopic cancer can have a heyday.

Chemo is used to kill any remaining cells after removal; it is usually targeted towards the infected organs at this stage. One method, hepatic artery infusion for metastatic colon cancer, targets the chemo straight into the liver. Unfortunately, that weak spot doesn’t last forever. Cancer cells often “learn” how to reverse the gene-silencing process. By stripping methyl groups from the gene, they re-activate the survival, anti-cell death pathways, rendering themselves invincible to chemo drugs. At the same time, though, they retain many of the harmful gene mutations acquired during their wild, rapid-growth days. They become cancer cells resistant to chemo. This does not mean radiation and chemotherapy don’t work. It does mean that additional new treatments will be needed. Therefore, you must be prepared, and to know what treatments will work best, you need to know how cancer cells survive radiation and chemo.

What is the place of chemo? As an adjuvant to surgery for colon cancer it confers an absolute survival benefit of less than 5%; in colon cancer it is largely palliative, improving quality of life and lengthening survival by 6-8 months. Most cancer patients develop a resistance to their chemo treatments. The prevailing belief in cancer therapy is that retreatment with a given drug after the emergence of resistance is ineffective.

The keys may be a protein called HIF (hypoxia-inducing factor), the chemokine receptor CXCR4 and FAS (fatty acid synthase) a key lipogenic enzyme catalyzing the terminal steps in the synthesis of fatty acids. Radiation and chemotherapy do kill some solid tumor cells, but in the cells that survive, the therapies drive an increase in a regulatory factor called HIF (hypoxia-inducible factor), which cells use to get the oxygen they need by increasing blood vessel growth into the tumor. Solid tumors generally have low supplies of oxygen, and HIF helps them get the oxygen they need. Both GenisZym and BroccoZym inhibit HIF transcriptional activity. We will discuss in more detail later.

HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms.

Targeting the hypoxia-inducible factor (HIF) pathway in cancer.

Expression levels and significance of hypoxia inducible factor-1 alpha and vascular endothelial growth factor in human colorectal adenocarcinoma.

Effect of HIF-1 modulation on the response of two- and three-dimensional cultures of human colon cancer cells to 5-fluorouracil.

Radiation-induced HIF-1alpha cell survival pathway is inhibited by soy isoflavones in prostate cancer cells.

Antiangiogenic activity of genistein in pancreatic carcinoma cells is mediated by the inhibition of hypoxia-inducible factor-1 and the down-regulation of VEGF gene expression.

Sulforaphane inhibited expression of hypoxia-inducible factor-1alpha in human tongue squamous cancer cells and prostate cancer cells.

Inhibition of HIF-1 alpha and VEGF expression by the chemopreventive bioflavonoid apigenin is accompanied by Akt inhibition in human prostate carcinoma PC3-M cells.

Metastasis is the ability of cancer cells to spread from a primary site, to form tumours at distant sites. It is a complex process in which cell motility and invasion play a fundamental role. Recent studies have demonstrated that the chemokine receptor CXCR4 plays a crucial role in organ-specific metastasis formation. CXCR4 is a chemokine receptor frequently overexpressed on primary tumor cells. Organs to which these cancers metastasize secrete CXCL12, the unique ligand for CXCR4, which stimulates invasion and metastasis to these sites. Both GenisZym and BroccoZym inhibit CXCR4 activity too.

Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells.

CXCR4 regulates the early extravasation of metastatic tumor cells in vivo.

Modulation of CXCR4, CXCL12, and Tumor Cell Invasion Potential In Vitro by Phytochemicals.

Why are HIF, CXCR4 and FAS suddenly a big deal? These are the key to different ways of looking at cancers. As previously discussed, recent data has demonstrated that fatty acid metabolism plays a critical role in cancer. Fatty acid synthase (FAS) is highly expressed in many kinds of human cancers, including colon cancer. Government, university, and drug-company researchers are racing to develop new drugs that inhibit HIF and FAS. But patients may not have to wait that long. Fortunately, we have novel, natural compounds that can selectively inhibit FAS activity without affecting fatty acid oxidation and demonstrated that these compounds effectively inhibit growth of human colon cancer without causing toxicity.

The overactivation of FAS synthesis in cancer cells is induced by the PI-3K/AKT pathway. This pathway is always active in cancer cells, providing growth stimuli and protection from apoptosis. The inhibition of FAS, by a mechanism yet to be explained, further inhibits AKT activity. It is the inhibition of AKT activity by the FAS inhibitors that actually induces apoptosis.

SinnolZym, a natural inhibitor of FAS, inhibit growth and induce apoptosis in the metastatic colon cancer.

High-level expression of fatty acid synthase in human prostate cancer tissues is linked to activation and nuclear localization of Akt/PKB.

Positive feedback regulation between AKT activation and fatty acid synthase expression in ovarian carcinoma cells.

Role of the phosphatidylinositol 3′-kinase/PTEN/Akt kinase pathway in the overexpression of fatty acid synthase in LNCaP prostate cancer cells

Why does tumor-associated fatty acid synthase (oncogenic antigen-519) ignore dietary fatty acids?

Metabolism and cell shape in cancer: A fractal analysis.

Saturated fatty acid metabolism is key link between cell division, cancer, and senescence in cellular and whole organism aging.

Fatty acid synthase inhibitor cerulenin suppresses liver metastasis of colon cancer in mice.

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