Cancer is an Age-dependent Stress-induced Breakdown of Tissue Homeostasis

Cancer arises from stress-induced breakdown of tissue homeostasis: Part 4

This is Part 4 of a four-part article. Part 1 provides a general introduction for the whole article. Part 2 is a critical review of the randomized trials of cancer treatments and screening.  Part 3 is a critical review of the dominant paradigm of cancer as mutation-centric “metastasis”. The whole article is available as a single PDF file on ResearchGate. The article was presented at the University of Ottawa on November 21, 2015, and is available in video as parts One and Two.

Part 4: Cancer as age-dependent stress-induced breakdown of tissue homeostasis

Allow me now to describe my tentative picture of cancer, which is consistent with the observations about the nature of common cancers, while being as conceptually simple as possible. The model is predictive and therefore testable, and if it is correct, then it should be a guide for prevention and treatment, and for new experimental designs of lab models for use in research.

In essence, tissue homeostasis, that is, the dynamic preservation of organ shape, structure, and associated function, is a daunting task. The organ, like the body, must preserve its shape and internal structure, in the face of continued cell replacement, cell assignment, attack, repair, and a changing and fluctuating biochemical environment of the organ imposed by the whole body in interaction with its outside world (such as the office cubicle environment, the lunch counter, etc.).

On a given tissue, especially a surface tissue of the organ where there is direct contact with the extra-organ world, things go momentarily and locally wrong all the time. These localized mishaps spill over and grow until corrected, within a certain response and repair time. As such, we can postulate that for a given tissue in a given mean extra-organ environment, there will be a mean steady-state ((A “steady-state” condition is a condition that does not change with time or in which change in one direction is continually balanced by change in another. The steady-state condition occurs after some response time following a change in causal factors (here, following a significant change in the tissue’s biochemical environment).)) nodule or “tumour” size (diameter or volume). Call it the mean steady-state “tumour” diameter, DT.

Next, given the discussion about metabolic reactions to stress, provided in Part 1, ((D.G. Rancourt, “Cancer Arises from Stress-induced Breakdown of Tissue Homeostasis. Part 1: Context of Cancer Research, Dissident Voice, December 4, 2015.)) I postulate that in most circumstances the dominant control parameter relevantly affecting the extra-organ environment (the tissue’s environment, in all its possible biochemical complexity) is stress experienced by the whole organism (body), S.

In low experienced stress S, DT is small (1 mm or less, say) and the corresponding nodules are just the random fluctuations of organ-surface shape or roughness or density, and there are no symptoms — there is no cancer. On the other hand, beyond some critical stress, SC, the tumour itself, as a wound, induces additional growth that cannot be completely countered by the stressed tissue and a runaway growth occurs, corresponding to an infinite DT (in steady-state).

This means that the particular tissue or organ, in the particular mean extra-organ environment induced by a super-critical stress, will continuously grow one of more large tumours that will disrupt organ function and may physically cause body-system interferences (e.g., a large brain tumour physically compressing the cranium-encased brain).

I draw a graph of DT (y-axis) versus S (x-axis), for a given tissue in a given individual experiencing various degrees of stress, and I draw different curves for the different tissues, each tissue-specific DT v. S curve having its own SC for that individual (of a given age):

DT v S for 3 tissues w ScFigure 1: Steady-state nodule or tumour diameter versus stress experienced by the individual, for three different tissues or organs, each tissue having its own critical stress for that individual.

It is natural that different tissue types (organs) have different intrinsic stabilities, or capacities to maintain homeostasis. Slow-growth scantly irrigated tissue, with little environmental contact with outside elements and with low rates of stem-cell division, such as bone and cartilage will be relatively stable in shape, whereas high-turnover well irrigated tissues, with surfaces having significant environmental contact with outside elements and with high rates of stem-cell division, such as lung, mammary organs, and intestinal tract, will have high susceptibility to surface-shape instability. Thus, I imagine a sequence of tissue-specific critical stress values that follow the lifetime-stem-cell-division sequence introduced by Tomasetti and Vogelstein.

Next, I propose that the cluster of tissue-specific DT v. S curves moves to the left, towards lower experienced-stress tolerance, as the individual ages. Like this, where only the most unstable tissue is represented, for the sake of clarity:

DT v S for 3 ages w ScFigure 2: Steady-state nodule or tumour diameter versus stress experienced by the individual, for one tissue type or organ, and for three different ages of the individual. As the individual ages, the organs become more susceptible to a runaway loss of homeostasis.  

In this model, the cancer outcome arises from reciprocation between the tissue’s susceptibility to loss of shape-homeostasis (TSLH) and the level of stress experienced by the individual. Stress is subjective but its effect on the tissue’s complex biochemical environment is objective, in that it can in-principle be measured.

The TSLH will depend not only on stress-induced changes of the tissue’s environment but also on:

  • the intrinsic tissue-type properties (as measured by lifetime stem cell divisions) (Fig. 1);
  • the tissue’s background environment in the specific individual;
  • the tissue surface’s continued contact with homeostasis-process-mediating environmental substances (smoking in the lungs, diet in the digestive tract, sunlight on the skin);
  • regular intake of drugs and medications (such as Aspirin, see above); and,
  • the changes with age of both intrinsic tissue quality and the tissue’s background environment (Fig. 2).

Likewise, sustained stress may change tissue quality itself, not just the tissue’s biochemical environment.

Thus, for a given individual at a given period in his/her life, there will be a unique DT v. S curve for the tissue of most concern, with a corresponding critical stress SC. The individual’s persistently experienced stress level will either be lower or higher than SC, thereby determining whether or not the individual is developing a malignant cancer in the said tissue. If several tissues have critical stress levels below the individual’s persistently experienced stress, then the said several organs will form malignant tumours.

In this way, we understand “metastasis” as the simple consequence of the individual’s TSLH having gone supercritical for a cluster of tissue-specific DT v. S curves. There is no “spread”. The tumours develop simultaneously, each at their own tissue-specific rates, and there are also subcritical nodules everywhere… Carving out one or several tumours will not help. Radiation will not decrease TSLH, nor will toxic chemotherapy.

The resulting focus on prevention and treatment appears as three-fold:

  1. One branch addresses the societal and psychological factors causing the stress experienced by the individual;
  2. A second branch considers how TSLH might be altered towards lower susceptibility; and,
  3. The third branch considers how one might interfere with the feedback process that causes the runaway tumour growth, in a wound-healing-like process.

Branch-(i) probably is not aided by current treatment protocols, but the clinical attention given to certain patients even in administrating poison and radiation may sometimes have a net benefit?

Branch-(ii) might be affected by drugs that interfere with cellular capacity to acquire energy, such as dichloroacetate (DCA)? ((E.D. Michelakis et al. “Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer (Minireview)”. British Journal of Cancer (BJC), 2008, vol. 99, no. 7, pages 989-994.))

Branch-(iii) is probably affected by non-steroidal anti-inflammatory drugs (NSAIDs), which interfere with blood clotting.

The stress-induced TSLH model, or DT v. S model, allows conceptual room for “soft” (and “low-tech”) chemotherapy treatments because TSLH and feedback processes in tumour growth may be relatively easy to affect with small molecules that cause general biochemical changes in the tissue or tumour environment, related to coagulation, viscosity, pH, oxidative potential (pE), unknown chemical potentials, etc., without necessarily having a high-degree of metabolic target specificity.

Likewise, tackling the human stress side of the equation could have important “spin-off” benefits for society at large. The science of stress could use a boost.

Let’s end the “war on cancer” and start the peace process.

Denis G. Rancourt is a former tenured full professor of physics at the University of Ottawa, Canada. He is a researcher for the Ontario Civil Liberties Association. He has published more than 100 articles in leading scientific journals, on physics and environmental science. He is the author of the book Hierarchy and Free Expression in the Fight Against Racism. Denis can be reached at Read other articles by Denis.