Understanding Colon Cancer

Understanding Colon Cancer

Natural Strategies in Collaborative Cancer Care

by John G. Connor, M.Ac., L.Ac.

edited by Barbara Connor, M.Ac., L.Ac.

April 6, 2011

Table of Contents

Introduction
Natural Strategies in Collaborative Cancer Care
Background to Colon Cancer
Examples of Pathology and Blood Tests to Perform in Colon Cancer
Natural Compounds that Suppress Colon Cancer
Examples of Studies Supporting the Use of Natural Compounds in Colon Cancer
Natural Compounds that Target Growth Factors & Genes

Involved in Colon Cancer

Comprehensive Cancer Care Consultations
References

Introduction

Despite the use of surgical resection and aggressive chemotherapy, nearly 50% of patients with colorectal carcinoma develop recurrent disease, highlighting the need for improved therapies. (Patel & Majumdar 2009)

Individual studies estimate that as many as 69% of US cancer patients employ some type of complementary and alternative medicine, 76% of patients in a study of Midwestern cancer patients and 95% of radiation oncology patients in another study. (Wargovich et al 2010)

Barbara and I feel that the emerging concept and practice of targeted therapies which have a high specificity toward tumor cells provides a broader therapeutic window with less toxicity than the current chemotherapeutic agents. Theyare also often useful in combination with cytotoxic chemotherapyor radiation to produce additive or synergistic anticancer activity because their toxicity profiles often do not overlap with traditionalcytotoxic chemotherapy. Targeted therapies represent anew and promising approach to cancer therapy, one that is already leading to beneficial clinical effects. There are multiple types of targeted therapies available, includingmonoclonal antibodies, receptor tyrosine kinase inhibitors, and growth factor receptor inhibitors.

The wonderful thing about botanicals and nutritives is that they target many of the same growth factors, receptors and pathways as conventional drugs and chemos but in a gentler and less toxic way thereby allowing for decreased dosages in the more toxic chemos and drugs. One of the characteristics of plants is that they are pleiotrophic, i.e., they exert multiple effects. Therefore botanicals and herbs by their very nature not only enhance the effectiveness of chemos and drugs but they can reduce or eliminate many of their unwanted side effects.

There is an ever growing interest in treatment with natural compounds as an adjuvant cancer therapy along with conventional cancer therapy. (Virk-Baker et al 2010) For example the combination of a natural VEGF inhibitor along with lower doses of a pharmacological agent may prove helpful in reducing the unwanted side effects of chemotherapy. (Wargovich et al 2010)

Natural Strategies in Collaborative Cancer Care

The following is a list of natural strategies we employ and the issues we address in our approach to integrative cancer care:

· Alkalinity and Acidosis in Cancer

· Angiogenesis Blood Markers

· Appendix of Cancer Pathways

· Blood Tests for Cancer-Related Cachexia

· Blood Tests that Detect Various Polymorphisms that Relate to the Metabolism or Detoxification of Chemotherapy

· Blood Tests to Assess Hypercoagulation

· Bone Building Protocol for Bone Related Cancer

· Cancer and Sugar

· Chemotherapy and Predictive Bio-markers

· Copper Reduction Protocol

· Counteracting Cancer Related Cachexia with Natural Compounds

· Cytotoxic Herbs & Their Functions

· Factors that Increase the Risk of Blood Clots and Thrombosis.

· Glossary of Chemotherapeutic Drugs

· Growth Factors and Genes Involved in Cancer

· How Elevated Glucose and Insulin Promote Cancer

· Immunotherapy - Activating the Immune System with Natural Compounds

· Inflammatory Blood Markers

· Inhibiting Angiogenesis with Natural Compounds

· Managing the Side Effects of Chemotherapy with Natural Compounds

· Markers for Assessing Bone Health

· Natural Aromatase Inhibitors

· Natural Compounds that Act as Biological Response Modifiers

· Natural Compounds That Alleviate the Side Effects of Chemobrain

· Natural Compounds that are Radiation Protective or Synergistic with Radiation Therapy

· Natural Compounds that Downregulate HPV

· Natural Compounds that Downregulate IGF and are Insulinotrophic, and Anti-cancer.

· Natural Compounds that Enhance the Effectiveness of Paclitaxel

· Natural Compounds that Enhance the Effectiveness of Platinums

· Natural Compounds that Inhibit Multi Drug Resistance

· Natural Compounds that Lower Homocysteine

· Natural Compounds that Protect against Bone Cancer

· Natural Compounds that Protect against the Side Effects of Doxorubicin

· Natural Compounds that Reduce the Side Effects of Carboplatin

· Natural Compounds that Reduce the Side Effects of Paclitaxel

· Natural Compounds that Reduce the Side Effects of Platinol (Cisplatin)

· Natural Compounds that Reduce the Side Effects of Platinum Drugs

· Natural Compounds that Synergize with Doxorubicin (Anthracyclines)

· Natural Compounds that Target Growth Factors and Genes Involved in Cancer

· Natural Compounds which Hasten Recovery from Surgery

· Neuropathy and Cancer Pain Management

· Nutritional Support for Glutathione and Optimal Liver Detoxification

· Radiation and Cancer

· Reducing Inflammation with Natural Compounds

· Suppressing Hypercoagulation with Natural Compounds

· Surgery and Cancer

· Teas and Soups which Alleviate the Side Effects of Chemo and What to Eat During Chemo

· Tissue Pathology Reports

· Understanding the Mechanism behind Bone Metastasis

Background to Colon Cancer

· Colon cancer is one of the most common inherited cancer syndromes known. Among the genes found to be involved in colorectal cancer are: MSH2 and MSH6 both on chromosome 2 and MLH1, on chromosome 3. Normally, the protein products of these genes help to repair mistakes made in DNA replication. If the MSH2, MSH6, and MLH1 proteins are mutated and therefore don't work properly, the replication mistakes are not repaired, leading to damaged DNA and, in this case, colon cancer.

· Recent animal studies have suggested that colorectal tumors expressing a Ras mutation produce significant amounts of COX-2. This is of note since Ras mutations are involved in the production of late stage adenomas and eventual loss of chromosome 18.

· HER-2 protein is over expressed in 11% of colorectal cancer patients. The gene encoding HER-2 is amplified in 3% of cases. Over expression of HER-2 is not a predictor of outcome. However, patients who over express HER-2 may respond to Herceptin therapy. (Kavanagh et al 2009)

· MTHFR C677T genotype – (MTHFR - methylene tetrahydrofolate reductase). The MTHFR C7677T mutation appears to interact with folate in determining cancer risk, and there may be further interaction with riboflavin status. The effect of this mutation on cancer risk may be site specific in that individuals carrying the TT variant appear to be protected against colorectal cancer.

o Genetic variation in MTHFR but not TYMS may be useful for predicting toxicity from capecitabine in patients with advanced colorectal cancer.

Examples of Pathology and Blood Tests to Perform in Colon Cancer

· Pathology Tests

o BRAF – wild type is required for response to EGFR drugs.

o EGFR – (epidermal growth factor receptor) - If PTEN & Kras negative (wild) and EGFR positive then good response to Erbitux.

o ERCC1 – (excision repair cross-complementing factor 1)

o KRAS – (K-ras gene) - Kras mutation predicts poor response to anti-EGFR drugs, eg. Erbitux. (Jimeno 2009)

o p53 – if mutated it indicates poor response to DOX.

o TS - (thymidylate synthase)- If low then 5-FU will be useful (Saga 2003)

Examples of Studies Supporting the Use of Natural Compounds in Colon Cancer

· Combinations - We report here the efficacy of dietary antioxidants in combination with chemotherapy on tumor growth in the orthotopic COLO-205-green fluorescent protein (GFP) human colon cancer mouse model. The results of the present study therefore indicate enhancement of cisplatin efficacy by high-dose antioxidants in combination with fish oil for colon cancer progression and suggests the design of clinical trials for this regimen. (Ma H, et al 2009)

· Curcumin enhances the effects of 5-fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating the EGFR and IGF-1R signaling pathways. The inclusion of curcumin to the conventional chemotherapeutic agent(s)/regimen could be an effective therapeutic strategy for colorectal cancer. (Patel BB et al 2008)

· Green Tea Extract – is an effective supplement for the chemoprevention of metachronous colorectal adenomas. (Shimizu et al 2008)

· Isothiocyanates - Histone deacetylase (HDAC) inhibitors reactivate epigenetically-silenced genes in cancer cells, triggering cell cycle arrest and apoptosis. Recent evidence suggests that dietary constituents can act as HDAC inhibitors, such as the isothiocyanates found in cruciferous vegetables and the allyl compounds present in garlic. Broccoli sprouts are a rich source of sulforaphane, an isothiocyanate that is metabolized via the mercapturic acid pathway and inhibits histone deacetylase activity in human colon, prostate, and breast cancer cells. (Nian et al 2009)

· Omega-3 fatty acid (omega-3 FA) consumption has long been associated with a lower incidence of colon, breast and prostate cancers in many human populations. Human trials have demonstrated omega-3 FA to have profound anti-inflammatory effects in those with cancer. In vitro and small animal studies have yielded a strong body of evidence establishing omega-3 FA as having anti-inflammatory, anti-apoptotic, anti-proliferative and anti-angiogenic effects. The conclusions drawn from this review suggest that omega-3 FAs in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found principally in oily fish have potent anti-angiogenic effects inhibiting production of many important angiogenic mediators namely; Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), Platelet-Derived Endothelial Cell Growth Factor (PDECGF), cyclo-oxygenase 2 (COX-2), prostaglandin-E2 (PGE2), nitric oxide, Nuclear Factor Kappa Beta (NFκB), matrix metalloproteinases and beta-catenin. (Spencer et al 2009)

· Omega-3 PUFAs - This study was designed to examine the effects of a diet rich in omega-3-polyunsatruated fatty acids on a model of colorectal metastasis. It was found that the omega-3-polyunsaturated fatty acids from fish oil appear to decrease malignant metastatic tumor growth in the liver. (Gutt et al, 2007)

· Red yeast rice inhibited both tumor cell growths and enhanced apoptosis in HCT-116 cells. These results suggest that the matrix effects of red yeast rice beyond monacolin K alone may be active in inhibiting colon cancer growth. Red yeast rice with or without monacolin K may be a botanical approach to colon cancer chemoprevention worthy of further investigation. (Becker et al 2008)

· Resveratrol and pterostilbene Epidemiological studies have linked the consumption of fruits and vegetables to a reduced risk of colon cancer, and small fruits are particularly rich sources of many active photochemical stilbenes, such as resveratrol and pterostilbene. (Rimando and Suh 2008)

· Sulforaphane - Despite the reported cytotoxicity and apoptosis-inducing properties of sulforaphane (SF) in colon cancer cells, the details concerning individual mechanisms and signaling cascades underlying SF-mediated apoptosis remain unclear. Our results indicate that in SW620 cells SF acts to induce multivariate cascades including DNA-damage response pathway whose proapoptotic signaling is nevertheless reduced owing to the mutant status of p53 and caspase-2-JNK pathway which seems to complement and enhance p53-dependent signaling, however only in wild-type p53. Furthermore, both pathways require the active role of mitochondria and do not depend on generation of ROS, making SF an attractive chemopreventive agent whose antitumor properties should be further investigated in colon cancer. (Rudolf et al 2009)

· Vitmain D3 – Inhibits EGFR in colon cancer. (Tong et al 1999)

· Wogonin, from Chinese Scutellaria, was shown to induce apoptosis in human prostate and colon carcinoma cell lines by enhancing expression of tumor suppressing protein p53, and consequently enhancing expression of the p53 target-genes p21, p27 and PUMA. (Lee DH et al 2008)

Growth Factors & Genes Involved in Cancer

Examples of Natural Compounds that Target Growth Factors & Genes Involved in Colon Cancer

COX-2 (Cyclooxygenase-2) - is up-regulated in practically all cancers (75%). It is induced by phorbol esters, cytokines and growth factors, including TGF-beta-1 and bFGF. COX-2 is a potent inducer of angiogenesis by inducing angiogenic factors. Most common cancers with altered (amplified) COX-2 expression include: prostate, colon, breast, cervical, brain, gastric, pancreatic, lung, head and neck, kidney and bladder.

COX-2 is over-expressed in colorectal cancer (CRC), rendering tumour cells resistant to apoptosis. Selective COX-2 inhibition is effective in CRC prevention, although having adverse cardiovascular effects, thus focus has shifted to downstream pathways. (Doherty et al 2009) Positive expression of NF-kB was found in 72 (73.5%) colorectal cancer cases, whereas COX-2 expression was found in 48 (49.0%) cases. (Abdulla et al 2009)

3. Curcumin & n-3 fatty acids – inhibited pancreatic cancer by down-regulating COX-2. (Nutr. Cancer 2008)

4. Diosgenin – in fenugreek seeds – inhibits COX enzymes. (Wargovich et al 2010)

6. EPA and DHA in n-3 fatty acids from fish oils (Lee et al 2009) (Lim et al 2009)

The p53 tumor suppressor protein exerts its growth inhibitory activity by activating and interacting with diverse signaling pathways The highest frequency of p53 mutations reported in human cancers are lung, 56%; colon, 50%; esophagus, 45%; ovary, pancreas and skin, 44%; stomach, 41%; head and neck, 37%; bladder, 34%; prostate, 30% and breast, endometrium and mesothelioma, 22%.

p53 and VEGF were expressed in colorectal cancer (CRC) and had a predictive power of aggressive clinical behaviour in CRC. (Weekes et al 2009)

Researchers found that diets with a high glycemic load as well as diets high in red meat, fast food and trans-fatty acids may play an important role in the process of the p53 mutation that causes colon cancer. (Slattery et al 2002)

Barbara & I have been working in the integrative oncology setting for many years and have been collaborating closely with Donald Yance for 6 years. We are graduates of both his Level One and Level Two Professional Clinical Trainings - Fundamentals of the ETMS (Eclectic Triphasic Medical System) and Advanced Clinical Applications of the ETMS in Cancer Therapies.

Our cancer protocols are designed to work synergistically with targeted individualized medical treatment plans and emphasize the practice of healthy medicine aimed at the root source of ill-health. Our primary focus is to build your immune system, enhance your vitality, and to bring about harmony and balance throughout your body. The botanicals and nutrients will target a multitude of cancer pathways generally and specifically in each case.

Using chemo-sensitivity screening and tumor marker testing we will be identifying what are the most appropriate chemos or drugs to use which will have the greatest impact on the cancer and at the same time have the least negative impact on your health. If you need to undergo chemotherapy or radiation we will provide you with specific protocols to help alleviate the side effects as well as specific protocols to help enhance the effects of the chemos.

If you are interested in finding out more about how we work or if you would like to set up a phone consult please phone us at 919-309-7753 or email us at johnandbarbaraconnor@me.com.

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Compassionate Acupuncture & Healing Arts, 4501 Valley Forge Rd., Durham, NC 27705 Tel. 919-309-7753 Email: compassionateacu@nc.rr.com