Innovations in CANCER Prognosis & Treatment: Think MATRIX not the Cancer Itself

Cancer needs a Superhighway - The Tenascins

For decades cancer research and therapies have been aimed at defining mutations in cancer cells to better understand their aberrant behavior - uncontrolled growth and robust metabolism that fuels it. Mutations that are either promote growth (oncogenes) or fail to limit the processes (tumor suppressor genes). While this has been fruitful it does not explain all that is happening.

Recently, Nobel-winning strategies have utilized the immune system to improve upon our ability to kill cancer cells. While this has been a boon for therapeutics (Immune Therapies for Cancer) there is still the underlying question of why do they behave like they do, and can we get them back into control and out of the cellular “naughty chair”.

So what is missing?

One fascinating answer is the matrix, the extracellular proteins, glycoproteins upon which our cells live on. The lay public has tended to just consider the matrix has the stuff that holds us together and with aging loses its elasticity and gives us wrinkles etc. That mindset is behind the fad of eating collagen to replace damaged collagen in skin to the wrinkles disappear. The system is a little more complex than that.

Further the matrix is much more than collagen, although it is the most common extracellular protein. There is a whole range of proteins and glycoproteins (a mix of sugar residues and proteins) that not only contribute to form but affect cellular function.

The MATRIX tells the cells through its points of cellular contact where they are, how they should behave and lead them to where they should go.

In the case of cancer, this cadre of messages becomes disturbed to the point that not only does it facilitate excessive growth it makes it easier for the cancer cells to spread out into the tissues and beyond (metastasis).

One aspect that dictates the nature of the dance between cancer cells and the matrix upon which they are attached is a family of enzymes that degrade the matrix. Like Molecular Machetes they chop up the matrix into pieces allowing the cancer cells to spread out with ease. This family of enzymes are called the MMPs (Matrix Metalloproteases - basically enzymes that contain a metal and degrade matrix proteins). We most commonly associate these enzymes with inflammation and tissue injury where they degrade the damage areas ready for laying down new, healthy structures.

A feature of cancer is a smoldering, low level inflammation that stimulates a sustained expression of MMPs that then make it so much easier for cancer to spread. Of the family of MMPs, it appears that MMP-9 is one of the most reliable as an index of cancer prognosis and activity. A remarkable aspect is this characteristic hold true for aggressive brain cancers to blood cancers where the cancer cells just have to escape the bone marrow (Glioma & Lymphoma & MMP-9). Opening up channels in the matrix applies to both extremes of cancer presentation, and both are currently very hard to effectively treat.

Pharmaceutical approaches to this smoldering chronic inflammation have been clumsy and too specific. The focus for the last 2 decades has been on eliminating a specific mediator or cytokine e.g., TNFalpha or IL-6. While this can bring immediate impact it does not solve the root cause (pharmaceutical companies try to avoid that approach). The core problem of chronic inflammation is an alteration in gene switches that are controlled by oxidative stress. So if you block the master switch you can correct a vast number of genes and bring about a restored harmony.

Fortunately, certain botanicals are excellent at modifying these master controllers of gene expression, examples of which are curcumin (from turmeric) and my favorite Cats Claw from the Amazon Rainforest of which I have shown to be an effective suppressor of MMP-9 activation in inflammation (Cats claw & NF-kB ; Herbal-Leucine Mix & Matrix Health)

Beyond the MMP-driven means to chop up the matrix, the structural element composition actually change in cancer. An imbalance in the matrix structure is now considered a very powerful tool to determine prognostics.

Derangements in the matrix profile have a major influence on survival, prognosis & is now a feature of therapeutic innovations.

While collagen may be the primary extracellular protein the focus is on a small family of glycoproteins that you may have never heard of - The TENASCINS. Further, we now appreciate that the tenascins are important players in a variety of disorders, cardiovascular health and inheritable joint & mobility disorders (Tenascins & CV & Mobility Health).

In terms of CANCER, it appears that the problems center on excessive Tenascin C (Tenascin C & Cancer Prognosis) and a lack of Tenascin X (Loss of TNX as a Pan-Cancer Marker). These alterations in tenascin levels are not moderate or flippant, along with the elevations in MMP-9 they are becoming the most powerful predictors of survival and cancer progression. At the same time, they are pointing the way to new ways to approach cancer treatment. It is not just the cancer cells themselves but their contacts with their environment that is critical.

Progress is coming from these advances in the role of the matrix, as well as with advancing knowledge in epigenetics (the switches that control which genes are turned on or off - Epigenetic Control of cancer) and altered mitochondrial activity (the sources of cellular energy for the demanding, metabolic requirements of cancer cells.

Bottom Line: Cancer is not just about the mutations in cancer cells, but how these cells interact with their environment and outcomes may well be dictated by the matrix as much as the cancer cells themselves.