Cancer redefined … altered cellular metabolism, transformed tissue environment, dynamic, reactive, and reversible!
“Virtually every process in a cell is carried out by macromolecular complexes whose actions need to be perfectly orchestrated.”
Dynamic interactions of proteins in complex networks: a more structured view
Amelie Stein, et al., Institute for Research in Biomedicine, Barcelona, The FEBS Journal, 2009
“Epigenetic changes are potentially reversible, … are highly responsive to environmental influences (at the cell-level microenvironment).”
“Wounds that will not heal,” J Byun, K Garchner, 2013
Recent Discoveries
Research discoveries in recent years have revealed that we must reconsider how we approach cancer and chronic disease. For example, genetic research has demonstrated that cancer and its biology is quite different than current accepted understanding. By looking at cancer at the cell level, the tissue microenvironment, we can see that cancer should not be defined by its “hallmarks” (proliferation, invasion, DNA mutation, etc.). This perspective tended to present cancer as an “invader” to the body which needed to be killed. If we look at cancer as if it were a chronic disease, or more appropriately, as a wound, might we take a different approach to treating cancer, to heal instead of kill? Advances in genetic research in the last ten years have lead to an abundance of information regarding tissue biology occurring at the cell level. Cell function and its resulting signaling has been identified in great detail. A new science, a family of sciences, has emerged, and with it amazing revelations about chronic disease and cancer. The new science is the science of cell signaling.
In normal human physiology, the body compensates for disruptions. These disruptions, such as changes in temperature, physical activity, nutritional intake, injury, infection or disease, cause the body to respond and attempt to normalize function. If the body fails to normalize or compensate for the disruption, a more permanent state of injury and response occurs. We have come to define this process of continuing or unresolved injury-response as “chronic disease.” We now have the capacity to examine chronic disease at its most basic level, its origin, the disease microenvironment.
Chronic disease at the cell level is characterized by cells that are experiencing stress. The stress, real or perceived, can be from of a variety of types or sources. Each cell senses the stress factors and attempts to adapt in order to survive. In the process of each cell’s adaptation “signals” are emitted which are in turn, sensed by surrounding cells. When a sufficient number of cells are persistently experiencing stress and signaling becomes of a sufficient quantity, the signaling can reach throughout the body, become “systemic.”
Every cell, regardless of type, responds to stress in the same way.
When cell stress becomes persistent the cell makes a dramatic change. It modifies its own metabolism. Over time, if the cell does not recover and return to its normal metabolism, cell signaling is amplified with additional of new signaling to represent the elevated stress or damage. When a group of cells establish a more permanent condition of stress, the signaling becomes even more amplified to the point that some cells are injured. In chronic disease and cancer, rather than healing the injury, this altered disease microenvironment establishes characteristics and signaling that sustain and expand the disease state.
At the cell level, chronic diseases like cancers, possess the same characteristics, very similar physiology. Recent advances in disease research, disease behavior at the cell level, has opened the door to re-evaluate disease, to offer the opportunity to change the way we treat disease.
An “invader” that must be removed or killed?
Cancer is actually a chronic inflammatory disease,
“a wound that will not heal.”
Chronic disease and all cancers are actually diseases of cell microenvironment. It is important that we recognize this fundamental redefinition, to reconsider how we treat disease. Alterations in the cell metabolism, gene expression, structural modifications or DNA mutation are actually consequences of a diseased cellular microenvironment. This new understanding presents the opportunity to investigate the most basic causes of disease. In recent years, that investigation has been proceeding at a dramatic pace. Cell signaling pathways have been discovered and mapped in detail. These signals are comprised of micro-RNA, proteins, proteases, lipids, peptides and various other molecules. Cell signaling is always in response to the cells immediate environment and represent actual cellular functions.
“Cancer is a complicated disease that may develop in humans
over a number of years. Development of a tumor starts with a
normal cell that is transformed through the activation of
proto-oncogenes and the suppression of tumor suppressor
genes such as p53. The transformed cell no longer behaves
like a normal cell but begins to exhibit the properties of a
cancer cell. Such transformation in the cells makes them
self-sufficient in growth signals and resistant to anti-growth
signals, resulting in uncontainable proliferation. In addition,
these cells are able to avoid apoptosis (normal programmed
cell death), resulting in tumor growth. This whole process of
transformation may take 10–20 years.”
Targeting Inflammatory Pathways by Triterpenoids for Prevention and
Treatment of Cancer
R Vivek, et al., MD Anderson Cancer Center, 2010
Cancer is an inflammatory chronic disease. Chronic diseases do not occur overnight. Some are even passed along through generations via “epigenetic” modifications. What makes chronic disease, “chronic?” Chronic disease, to exist for years, or even generations, logically must impart permanent characteristics within the cellular environment. These permanent changes interfere with the body’s own attempts to heal or repair injured tissue. Over time, an independent cell environment is created, with each cell having an altered metabolism. This disease environment escalates with an accelerated level of damage signaling and resulting response. A variety of complex abnormal cell signaling exist. The signaling is very reactive, is progressive and is highly redundant with complex feedback and feedforward signaling mechanisms. The environment exists in a constant state of injury and response in an attempt to heal the tissue.
Along with a new understanding of disease, there has been tremendous advancement in our understanding of the biological mechanisms of nutrition. In the chronic disease microenvironment, every cell experiences altered metabolism. Nutrition is the only natural resource the body has to combat disease. For thousands of years, history has demonstrated that nutrition can heal chronic diseases and cancer. With the introduction of the science of cell signaling, we can now confirm the mechanisms of how nutrition can “heal” diseases. Nutritional “agents” have been identified. These agents have been shown to modify the disease state at the cell level, to recover cell metabolism, to stop the cycle of stress and response. Methods to improve the effectiveness or bioavailability of nutritional agents have also been studied and developed. These bio-enhanced, nutritional agents are now available commercially within and exponential increase available within the few years!
Most, if not all of these nutritional agents have been in use for thousands of years across the world. Applied in all cultures for the treatment of diseases, including cancers. What is different now, is that these nutritional agents are more bioactive and we now actually know why they are effective. How they function at the cell level.
“The last decade has witnessed rapid advancement in the
development of nano-chemopreventive technology with
emergence of many nano encapsulated formulations
of different dietary anticancer agents.”
Progress in Nanotechnology Based Approaches to
Enhance the Potential of Chemopreventive Agents,
L Muqbil, et al, 2011
At Signal Physiology, we have traced the development of understanding of disease and nutritional agents for many years. Recognizing the potential of this new understanding, it becomes apparent that new protocols must be developed to apply and track the progress of these new agents. It is a very exciting time in medical research, no less than a revolution in medicine.