One of the most common questions I get from patients with cancer is "how did I get it?" This is a very important question but a very hard one to give a precise answer to in any particular case. Often, a patient will attribute the disease to poor lifestyle choices such as, unhealthy diet or cigarette smoking. Yet, this cannot be the complete answer since there are many people who engage in smoking and other toxic lifestyle choices but they do not develop cancer. On the other hand, there are patients who are astonished that they could have developed cancer since they have a very healthy lifestyle i.e. eating organic foods, no junk food, red meats, low fat high fiber diets, take all their vitamins and have little emotional stress. Obviously, the answer to how cancer develops is a complex one with many factors.
In the following discussions, we will look at current theories on the geneses of cancer as well as exploring some less known ideas on how cancer evolves. These considerations have more than theoretical importance since knowledge of the fundamental nature of cancer has direct implications for treatment options.
The current scientific thought on the cause of cancer focuses on the individual cell and particularly the DNA. It is known that alterations in the DNA can lead to loss of regulation in the growth process at the cellular level. Genes known as onco-genes and tumor suppressor genes control how cells divide and play a vital, but not exclusive role in the evolution of cancer. Proto-oncogenes exist in all cells. When these genes undergo damage from toxins or free radicals they may become onco-genes and promote unregulated cell growth. On the other hand, tumor suppressor genes are down regulating cell growth and if they are damaged the breaks on cellular growth are removed and this can also lead to uncontrolled growth. There is evidence that viruses may cause cancer by either introducing an onco-gene into the DNA or damaging proto-onco genes or tumor suppressor genes. Most cancers in humans are not thought to be of viral origin.
This focuse on cancer being caused by cellular damage to the genetic code has lead to the use of therapies that kill abnormal cells (i.e. chemotherapy and radiation).
The problem with this is that although damage to the DNA may be necessary to establish cancer it is only one of, and probably not the most important, of a number of factors that ultimately lead to the development of the state of cancer. The fact is that everyday it is estimated that the genetic code is damaged thousands of times, anyone of which could lead to cancerous changes. It is also been observed that cancer exist in the prostates of many older men and the breast of many older women who die of causes other than cancer. In fact some studies demonstrate that as many as 30-40% of men over 40 may harbor some prostate cancer that never becomes clinically evident. It is thus thought that the development of cancerous changes at the cellular level is common and even normal and not sufficient in and of themselves to produce the clinical syndrome of cancer.
The cause and therefore the solution to cancer is a complex interaction of the cancer cells and the environment that these cells exist in. It is this critical factor of the environment or terrain that has not been adequately addressed by current models of cancer therapy. We have developed excellent cytotoxic therapies (chemotherapy and radiation) that are capable of shrinking tumors to the point that they are no longer clinically apparent. In spite of this, most of these therapies have not been demonstrated to prolong life for any significant period. The problem is not that we do not have good agents that can kill cancer cells because we do. It should then be an obvious conclusion that since killing cancer cells has not translated to prolonged survival, that killing cancer cells is not the ultimate answer to cancer.
Many researchers have put forth that it is not cancer cells that are the primary abnormality but the interaction of these cells with the body's immune system and metabolism. In order for cancer to become lethal it must progress through various stages. These stages are initiation, proliferation, invasion, metastases and finally shock.
Many years ago, Dr. Revici recognized that the development of cancer required the successive breakdown of the body's defenses such that each level of organization in the body needed to be impaired in order for the cancer to progress from one stage to the next. He divided the body into the following organizational hierarchy: subnuclear, involving the DNA; nuclear, cellular, tissue, organ, and system. Each of these levels of organization had some independence from each other being separated by a barrier of some sort. For example the cell maintains its identity because the cell membrane separates it from the rest of the body. Each level of organization has its own defenses and in order for cancer to proceed from one level to the next the respective defense mechanism must be impaired.
Initiation is what transforms the cell from a normal cell to one that can potentially lead to cancer. This occurs when the DNA is damaged and eludes the body's repair mechanisms and therefor corresponds to what Dr. Revici called the precancerous phase. As previously mentioned, free radicals, chemical carcinogens, radiation or viruses can cause this process. Now that this initial damage exist, the stage is set so that other environmental, metabolic and immune factors can cause the cell to grow in an abnormal fashion.
Cancer cells may not grow quicker than normal cells, in fact some grow slower. What is often characteristic of the growth phase is that the cells do not die in a timely fashion and therefore cell growth will out pace cell death. Dr. Revici spoke in terms of anabolic and catabolic metabolism being out of balance as the primary factor in the abnormal growth cycle. He recognized that metabolic function needed to be in balance in order for health to exist. In the case of cancer, he showed that the anabolic factors were out of proportion when compared to catabolic ones and hence a cell was pushed in the direction of longevity and growth. This can be a healthy response when the body is trying to heal from damage such as trauma or at the cellular level from free radical injury. If the body is not able to repair the damage and the anabolic conditions persist in the healing effort, the result may lead to abnormal growth if the cell is already predisposed. This is what Dr. Revici called the noninvasive phase of cancer, also known as cancer- in –situ. In this stage, the abnormality is manifest in the organization of the cells in the tissue. In many respects, the cells appear normal except for the nucleus which is more immature in relation to other cells in the tissue.
In the invasive phase, when the imbalance has progressed to the cellular level, the cells infiltrate the adjacent tissues. In order for the cells to invade neighboring tissue the defenses of this tissue have to be impaired. This often involves a break down of the connective tissue that separates groups of cells. When this occurs cancer cells secrete chemicals known as proteases which are enzymes that can break down the proteins in connective tissue. In addition, the tissue being invaded seems to be deficient in its ability to produce protease inhibitors, which could prevent the break down of the connective tissue barrier. As the cancer continues to invade adjacent tissues the local environment in the area of invasion becomes more acidic causing pain. According to Dr. Revici's conception, the onset of pain is characteristic of imbalance at the tissue level.
When cancer spreads to distant sites it is said to be metastatic. Cancer cells disseminate throughout the body via the blood or lymphatics. The release of cells into the body is not in itself sufficient to allow new tumors to develop in other organs. It is known that the initial tumor is capable of releasing millions of cells into the general circulation every day, yet only under certain conditions will these cells implant in distant organs and grow to form new tumors. The following must occur for cancer to successfully establish itself in a distant site: First, the cells must detach themselves from the primary tumor and invade a lymphatic or blood vessel. Once inside the lymphatic or vascular system the cell must evade the immune system. If the cell manages to get this far, it has to transverse the vessel again to enter the new location. When the cell invades, the new organ conditions must allow for the cancer cell to divide and establish a blood supply. If anyone of these steps is interfered with, cancer will not become metastatic. Dr. Revici considered the occurrence of metastasis to be the beginning of the preterminal phase of cancer. In this phase biochemical changes occur in organs that may not actually have tumors themselves. As the cancer progresses, metabolic function becomes increasingly deranged. When the systemic level is reached, the metabolism is so out of balance that the tumors become of secondary importance in the overall condition. The predominant symptoms consist of fatigue, anorexia, weight loss and increasing withdrawal from daily activities. Finally, a state of shock ensues in which the patient is primarily catabolic eventhough the cancerous tissue is anabolic. At this point, it is these systemic changes that must be addressed even before treating the tumors, since it is these metabolic changes that may ultimately lead to death.
As can be seen the development of the clinical entity known as cancer is much more involved than the changes that occur on the nuclear and cellular levels. As long as the current approaches to treating cancer focus on the destruction of cancerous cells the results will not be satisfactory. The cancerous cell and tumor should be viewed more as a symptom of derangement in the metabolism and immune system, rather than the primary focus. When we look at the big picture of the nature and evolution of the cancerous condition, the treatment options are increased. We need to increase our efforts to alter the metabolism and physiology of the organism so that it is not supportive of the anabolic metabolism of cancer. If cancer remains in the nuclear or even cellular phase it will not present a problem to the individual. Therefore the goals of treatment may not be to eradicate every cancer cell at all cost, but to establish a physiology that allows the rest of the body to co-exist with the cancerous cells.