Innovative Treatments to Successfully Target Malignant Pleural Mesothelioma

Malignant Pleural Mesothelioma (MPM) is the most common type of mesothelioma with past asbestos exposure representing the major risk factor. While the search for new therapies that target the genes and processes driving MPM has been slow, two new approaches, which are immediately available to you, are showing significant improvements over standard treatment in clinical trials.

Before we discuss these enhanced treatment options, we must first briefly explore two key aspects of MPM progression: Angiogenesis and Epigenetic Regulation.

Angiogenesis:

You've likely heard of Angiogenesis. It is the physiological process that tumors use to recruit new blood vessels in order to sustain their continual growth. They do this by manipulating the over-expression of genes that initiate and direct the growth of new, leaky blood vessels from existing ones. This new supply of blood not only allows the tumor to grow, but also provides a mechanism for the tumor cells to metastasize (travel through the body).

The process of angiogenesis is governed by its own unique combination of genes, separate from those involved in the normal formation of new blood vessels (a process known as vasculogenesis). This, it turns out, provides us with an opportunity for successful treatment through the targeting of these unique gene combinations.

One of the most specific and critical regulators of angiogenesis is the family of vascular endothelial growth factors (VEGFs), which regulate endothelial proliferation (the formation of new blood vessels), blood vessel permeability, and survival.In MPM,over-expression of VEGF is common and correlates with lower remission rates and reduced overall patient survival. Clearly, effectively targeting VEGFs would result in limiting the blood supply to tumors thus successfully prohibiting their growth. And that's just what we are seeing in current clinical trials. (More on that in a bit.)

Epigenetic Regulation:

A significant development in MPM treatment involves studies that focus on manipulating the processes of gene regulation, commonly referred to as epigenetic regulation. In MPM, tumor suppressor genes (the genes that, when functioning properly, naturally prohibit the growth of tumor cells) are silenced due to three key forms of epigenetic regulation:

1. Removal of acetyl groups by histone deacetylases (HDACs);

2. Inhibition of histone acetyltransferases (HATs), which add acetyl groups; and

3. Addition of methyl groups by DNA methyltransferases (DNMTs).

In MPM, the over-expression of HDACs coupled with the inhibition of HATs is considered a key process that leads to disease progression. The over-expression of DNMTs occurs in most cancers.

The benefit of targeting epigenetic processes is that they are reversible. Unlike a mutated gene which cannot be reactivated, it is possible to reactivate tumor suppressor genes that have been silenced by epigenetic processes. Thus, effective treatment must include some process whereby tumor suppressor genes are supported to maintain their function and reactivated in cases where they have already been silenced.

To this end, there are numerous clinical trials currently exploring the use of unique combinations of drugs to inhibit the silencing of tumor suppressor genes and to stop the flow of blood to tumors. Current clinical trials using HDAC and VEGF inhibitors are showing significant benefits in patient survival. For example, Vorinostat, an inhibitor of HDACs, has recently been shown to be beneficial for advanced mesothelioma patients whose cancer has progressed after standard chemotherapy.

The continued development and incorporation of these new drugs as part of standard treatment will undoubtedly be realized over the next few years. In the meantime there are some very simple and effective natural measures that you can take immediately that will directly and powerfully influence the growth of cancer.

While clinical trials provide the basis for current molecular-targeted therapies, plant phytochemicals (also known as: Nutraceuticals) provide an exciting option as an additional means of gene regulation.

Science has identified the following nutraceuticals as having a significant effect in slowing the mechanisms involved in MPM progression. Thus it is imperative, as part of your treatment protocol, that you ensure these substances are a part of your daily diet in the appropriate combinations.

The following section is a list of nutraceuticals that have been shown to directly affect epigenetic regulation and angiogenisis in various cancers.

In order to inhibit DNMTs to maintain tumor suppressor gene function, we must consume the following foods:

Apigenin (Parsley, Thyme), Curcumin (Tumeric, Ginger, Mustard), EGCG (Green Tea, Nutmeg)

Genistein (Soy), Resveratrol (Red Wine, Grape Skins), Sulforaphane (Broccoli, Brussels Sprouts, Cabbages)

In order to inhibit HDACs to maintain tumor suppressor gene function, we must consume these foods:

Allyl Mercaptan(Garlic), Curcumin (Tumeric, Ginger, Mustard), Genistein (Soy) Sulforaphane (Broccoli, Brussels Sprouts, Cabbages)

In order to activate HATs to reactivate tumor suppressors, we must regularly consume these foods:

Curcumin (Tumeric, Ginger, Mustard), EGCG (Green Tea, Nutmeg), Genistein (Soy)

In order to inhibit VEGFs to prevent further angiogenesis, we must ensure that these substances are a part of our daily diet:

Curcumin (Tumeric, Ginger, Mustard), EGCG (Green Tea, Nutmeg), 6-Gingerol (Ginger)

In Conclusion:

There are many molecular pathways and genes involved in MPM. Above we have explored just a few. However, including a daily diet of the nutraceuticals listed above will go a long way to improve your statistical chances for remission and disease prevention, as these nutraceuticals are revealing themselves to be significant in the treatment and prevention of many forms of cancer.

Given the success of current clinical trials being conducted using molecular-targeted therapies this is also an important avenue to consider as an adjunct to standard treatment. Many clinical trials can be accessed from your home town through your current treatment specialist after a brief registration and testing process.

It is essential that you talk to your doctor before considering any changes to your diet as these nutraceuticals, while typically enhancing of any standard therapy, can interfere with prescription drugs.

If you would like more information on the use of nutraceuticals to enhance your life-expectancy or to have a personalized nutraceutical diet prepared for you, we welcome you to contact us @ contact@ctoam.com. We are also happy to arrange to consult with your treatment team to share the most current information on enhanced treatment options and clinical trial access with them.

Patient Resources:

The Mesothelioma Center - The web based resource also provides free support services for patients and families world-wide. For additional information please visit www.asbestos.com or call (800) 615-2270.

About the Author:

Alex Rolland is a cancer researcher, educator, and CEO of Cancer Treatment Options and Management ( http://www.ctoam.com/ ). CTOAM is a personalized cancer research company that specializes in using the most current peer-reviewed scientific research on cancer diagnostics, enhanced treatments, nutraceuticals, and clinical trials to educate patients on the treatments and diets that will provide the best statistical chances for longstanding recovery.


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