When a Cell goes Bad - How Cancer Starts
by Michael Guthrie, R.Ph.
Robert Weinberg’s book “One Renegade Cell” makes for fascinating reading. Weinberg’s book emphasizes how many bizarre things must happen for a cancer cell to be produced, implanted and eventually, silently, and mysteriously grow to such proportions that it threatens the very existence of its host. With this in mind, we will briefly explore the various phases which neoplasms go through on their way to becoming a life threatening malignancy.
Nowhere have I seen this summarized better than in John Boik’s remarkable book “Natural Compounds in Cancer Therapy. (www.ompress.com)” Within its 500 pages are thorough explanations of the molecular biology of cancer, tumor immunology, and of course splendid research on promising natural compounds (including their mechanisms of action). Quoting directly from Mr. Boik’s book, we see how healthy cells are supposed to act.
“Imagine a healthy tissue containing thousands of cells. Each cell serves the greater good, which is the continuation of a person’s life. Each cell is programmed so that when the cell is old or no longer needed, it dies a peaceful and timely death. This death is call apoptosis. All cells are in communication, which allows for the smooth repair and replacement of tissues and other aspects of cell behavior. Communication takes place either indirectly, via exchange of messenger compounds such as hormones and growth factors, or directly via cell-to-cell contact. Contact allows cells to respond to the “feel” of neighboring cells, via cell adhesion molecules, and to exchange messenger molecules through cell-to-cell portals called gap junctions. With the help of proper communication, appropriate cells proliferate when new cells are needed, and when enough new cells have been produced, cell division stops.”
Cancer cells don’t act like the healthy cells described above. Let’s discuss the pathogenesis of cancer.
Initiation: The transformation of a normal cell into a neoplastic cell occurs in response to one or more initiating factors. The primary initiating factors appear to be chemical carcinogens, viruses, and ionizing radiation. No matter what the source of insult, the result is damaged DNA, leading to mistakes when the cell divides with the eventual outcome of transformation into a cancer cell (neoplasm). Actually mistakes in DNA replication happen all the time and our cells are equipped to handle this by either repairing the DNA, or by the cell committing a programmed cell death (apoptosis). Therefore, in order for the cell to become cancerous, it must escape these protective mechanisms.
Proliferation: In order for the individual cancer cell to propagate itself by division, it must also overcome numerous obstacles. Actually, cancer cells do die, and the only way for the individual cells to become a tumor is for the rate of cell growth to overcome the rate of cell death. It is believed that the cancer cells achieve their growth through the initiation of stem cells. Stem cells are abundant in actively growing tissues, such as in tissue repair, but they are controlled. In neoplasms, the stem cells proliferate unchecked. Also, in cancers, the daughter cells are not fully differentiated, that is they do not exactly match the cell of origin. For example a malignant liver cell is not exactly like a liver cell; it is a mutant. Complementary approaches to cancer treatment employ natural agents that stimulate redifferentiation of the DNA.
Angiogenesis: Tumors could only reach a certain size before they would exhaust themselves of nutrients if it were not for angiogenesis. Simply put, this is the tumor’s ability to coax the body to supply it with a vigorous blood supply. The mechanism by which this happens is complex, and will be the subject of an entire article in the near future. A number of natural products interfere with angiogenesis and prescription drugs are in development that target angiogenesis.
Invasion: Invasion is one of the hallmark characteristics of a cancerous tumor. Normally different types of tissues have very well defined borders which is why you won’t normally find skin cells growing in deep muscle, or liver cells growing in the stomach. The amazing human body uses a myriad of mechanisms to maintain order and boundaries, yet somehow cancerous tumors have the ability to invade and pierce these protective barriers. The biochemistry by which this happens is complex and in many respects not well understood.
Metastases: Metastases is another “hallmark” of cancerous tumors, and involves the ability of the primary tumor to “seed” via the blood stream or lymph system to distant sites where new colonies are established. Metastasis is actually not very efficient. In fact in a study of patients with renal cell carcinoma, it was found that their tumors released from ten million to one billion cancer cells into the bloodstream every day, but only 20% developed distant tumors. (Boik, “Cancer and Natural Medicine, 1996) .
Understanding of the mechanisms via which cancer cells grow and metastasize is leading towards promising complementary approaches. Every stage of development mentioned in this article can be addressed via natural products and many by prescription drugs.
The Genetics of Cancer
Cancer is fundamentally genetic, in that it arises from mutations distorting the information contained in genes. For the most part, the genetic dysfunction is not inherited, but acquired during life. In fact, probably less than 10% of cancer patients have a strongly predisposing inheritance and another 20 to 30% have a moderately predisposing inheritance (Ross, “Introduction to Oncogenes and Molecular Cancer Medicine,”1998).
All of this genetics talk can become quite confusing, so we’ll try to keep it as simple as possible. There is no doubt that some cancers are strongly associated with a genetic predisposition…and let’s reemphasize the word predisposition. Along with the predisposition, there almost always has to be subsequent events that damage the DNA of a cell for that cell to begin its course towards malignancy. In fact the damage occurs with specific genes that you will be hearing much more about: proto-oncogenes, and tumor suppressor genes.
Perhaps the most notorious inherited mutations are those of the genes BRCA1 and BRCA2. Mutation at either site carries a 70% probability of breast or ovarian cancer BUT, 95% of the time, breast cancer occurs without this mutation.
The press has recently been buzzing with news of the human genome project. Basically, scientists are mapping the approximately 50,000 genes that are present in human DNA. About 100 of these genes are now known to be proto-oncogenes (Ross, 1998). These genes are very important in the process of producing growth factors that assure that cells grow and multiply especially during fetal growth. Many of these proto-oncogenes are normally “turned off” like a switch. The turning on of genetic switches is referred to by scientists as the “expression” or “over-expression” of the gene. When proto-oncogenes are mutated they become oncogenes, and the switch changes to the on position. Often a whole series of these genes become activated into oncogenes (Dollinger, “Everyone’s Guide to Cancer Therapy,” 1997).
If and when proto-oncogenes misbehave, the damage is normally arrested by another type of gene, called a tumor suppressor gene. Many have heard of the P53 gene. This is a tumor suppressor gene. So far about 20 tumor suppressor genes have been identified. In the case of p53, we have a remarkable smart gene. Somehow this gene detects when DNA has been damaged. In this case, p53 slows down the cell cycle and allows the DNA to repair itself. If that doesn’t happen, the p53 gene instructs the cell to commit suicide (apoptosis).
The dynamics of proto-oncogenes and tumor suppressor genes usually create a regulated and controlled environment of cell growth. In the case of cancer, something, in fact many things have gone terribly awry.
On a final note, it is interesting to note that it appears that proto-oncogene defects are not inherited. Damage to the proto-oncogene occurs after birth. Conversely, there is a genetic link to many tumor suppressor genes, such as p53. Still, this defect alone does not cause cancer. Further DNA “hits,” occurring throughout one’s lifetime are required to permanently shut down the p53 gene.
Unraveling of the genetics of cancer is paving the way for novel treatments such as gene therapy. Even now, scientists are finding that certain natural products such as the herb andrographis paniculata may re-express the p53 gene when it is damaged. IP-6 appears to have similar “reparative” effects.