Methods of Treatment
In general, chemotherapy is a treatment that uses chemical agents to destroy all dividing cells. Therefore, chemotherapy is a non-specific, non-molecular treatment. Most chemotherapy agents kill cancer cells by interacting with the DNA synthesis or function of the cell. The chemical agents differ in the way this occurs in the cell cycle. Some major types of agents are antimetabolites, plant alkaloids, alklyating agents, antitumor antibiotics, and steroid hormones. Chemotherapy is typically administered through a vein, by mouth, or into a muscle. A common strategy of chemotherapy treatments is to administer the drug in intervals over an extended period. The side effects of chemotherapy include hair loss, nausea, vomiting, diarrhea, anemia, infections, fatigue, loss of taste buds, and destruction of the immune system.
Most chemotherapy operates on the principle that the most rapidly dividing cells will be the most susceptible to the drug. An example of this is the drug methotrexate, which is commonly used to treat cancer. Methotrexate is an anti-folate that is administered in high doses -- doses high enough to be lethal if not carefully monitored. Methotrexate works by competing with folate in the pathway that synthesizes thymine from uracil. Thymine is one of the four nucleotides required for the synthesis of DNA. Because the most rapidly dividing cells in the body -- the cancer cells -- have the greatest need for the synthesis of DNA, the cancer cells are the most vulnerable to attack by methotrexate. Again, however, this is a classic example of the approach in which one hopes the drug kills more cancerous than healthy cells. Methotrexate acts to inhibit dihydrofolate reductase, a key enzyme in the activation of folate to be used for thymine and purine biosynthesis. Methotrexate will bind to DHFR in place of dihydrofolate, therefore blocking the pathway at this step. This will cause misincorporation of bases into the tumor's DNA, which could result in the death of the cell. Other drugs, such as trimetrexate, are also being investigated for the same purpose. A problem with drugs such as methotrexate is that tumors often can be immune to this type of treatment. Because MTX's inhibition of DHFR is not complete, a tumor cell can compensate by producing large amounts of DHFR. This is accomplished primarily through additional copies of the gene coding DHFR present in the tumor's genome. Understanding the mechanism by which methotrexate works -- and that by which tumors can be resistant to the drug -- allows physicians to determine whether this is a potentially beneficial treatment. This determination is essential due to the potential toxicity of the drug.
A major advantage of chemotherapy is its ability to travel through out the body and attack widespread cancers, whereas surgery and radiation are confined to treat one area. The disadvantages of chemotherapy are the toxic side effects, the development of resistance to the chemical agents, and the need for other forms of treatment, in combination with chemotherapy, in order to cure the patient. These disadvantages are why molecular based treatments are becoming so valuable. Most molecular based treatments are designed specifically to destroy only cancer cells. Since molecular based treatments are specific they are not associated with the same toxic side effects as chemotherapy. In conclusion, increasing our understanding of the molecular basis of cancer would allow us to improve molecular treatments because unfortunately they can not perform efficiently without including other forms of treatments.
Bailey, Lynn, ed. Folate in Health and Disease. New York: Marcel Dekker, 1995.
Like chemotherapy, radiation primarily works by killing more cancerous than normal cells. Unlike chemotherapy, however, radiation is targeted to a tumor by only irradiating a certain part of the body. Chemotherapy targets cancerous cells primarily by virtue of the fact that they replicate faster than normal cells. Radiation involves a highly localized beam of radiation aimed at the tumor. Radiation treatment is considered based on the the location of the tumor and whether surrounding organs could also be adversely affected by the beam. Side effects include breakdown at the point of entry of the beam. After surgery, this ranks as the most common and effective form of cancer treatment.
There are two forms of radiation treatment: external beam and internal. External beam radiation consists of focusing a beam of high-energy waves (x-rays and protons have been used) at the tumor. Internal radiation therapy, or brachytherapy, entails the implantation of radioactive particles directly into the tumor. These particles are about the size of a grain of rice and are made up of radioactive isotopes like iodine 125.
Surgery is used to remove cancerous tumors. New microsurgical procedures using lasers and laparoscopic techniques are making surgery one of the safest forms of treatment. These techniques allow the physician to operate on the patient without actually opening the patient. Surgery is also one of the most common forms of treatment because it is an essential for diagnosis of the patient (i.e. biopsy). Although, surgery sounds like the most effective treatment it does have some disadvantages. For example, surgery can only treat a local tumor. In another words, if the patient's cancer were already widespread, surgery would not be extremely effective. Another disadvantage of surgery is the cancer cells left behind or escaping into the body by nicking the tumor. Consequently, additional treatments would be needed in order to cure the patient. The most effective treatment would be one that kills all the cancer cells remaining. Customarily, radiation and/or chemotherapy were the chosen treatments, however, these treatments have serious side effects. By developing molecular based treatments one could kill all the cancers cells left behind with less serious side effects. Therefore, a greater understanding of the molecular basis of cancer is necessary.
Immunological methods of cancer treatment are designed to encourage the body's immune system to attack the cancer. Under many circumstances, the body cannot recognize the cancer as a foreign body. As a result, the body is unable to fight the cancer naturally. The methods under this category are primarily molecular in basis; they take into consideration the differences between normal and cancerous cells and attack the cancer cells in ways which do not hard normal cells. Immunological method of treatment are still new and under development, but recent work seems to be promising.
Two specific immunological treatments are discussed in the following links:
According the the American cancer society, hormone therapy consists of "treatment with hormones, drugs that interfere with hormone production or hormone action, or surgical removal of hormone-producing glands to kill cancer cells or slow their growth." Methods such as these have been moderately effective in slowing the spread of breast and prostate cancer, among others. It involves the blocking of trophic factors, factors required for the prevention of cell apoptosis and death. This method is effective in reducing the number of differentiated cells, but it is limited in that it cannot kill the stem cells from which the tumor cells originate. For this reason, hormone therapy is not a cure. It is primarily used in cases when surgery and radiation are not viable options; for example, when the cancer has metastasized, and it would be impossible to surgically remove all cancerous cells. The goal of hormone therapy is to reduce the tumor in size until a patient is asymptomatic; a patient might be able to live in this manner for several decades.
Hormone therapy is also known as endocrine therapy, hormone ablation therapy, and anithormone therapy. There are three prerequisites for hormone therapy to be a viable option. First, the cancer-issuing tissue cannot be essential, since this form of therapy interferes with the growth of the normal cells as well. Second, the cancer must remain vulnerable to the treatment; many cancers can evolve over time and become resistant to this form of therapy. Third, the trophic factor which is blocked by the treatment must be tissue specific; if a factor which affected many tissues were inhibited, it would be difficult to control complications.
Prostate and breast cancer are prime targets for hormone therapy. Because the growth of prostate tumors is dependent on the presence of androgens -- male hormones such as testosterone -- hormone treatments for prostate cancer are aimed at reducing or eliminating these hormones. This is accomplished by one or more of several methods. The first is removal of the testes: the testes are the source of testosterone, and their removal eliminates testosterone. Monthly injections of luteinizing hormone-releasing hormone (LHRH) analogs work to accomplish the reduction of testosterone production without removal of the testicles. This treatment must be continued for the rest of the patient's life. This is often accompanied by treatment with anti-androgens, drugs which interfere with the body's ability to use what few androgens are produced. In a similar manner, certain breast cancers are estrogen dependent, and anti-estrogen therapies are common. Tamoxifen is one such anti-estrogen drug.
Other less-well-understood hormone therapies include interferon alpha and interleukin-2. Interferom alpha may act in one of two ways: first, it may act as a trophic factor for the body's immune system. Therefore it stimulates the growth of cells involved in the immune system, which is then stronger and more able to fight the cancer. Second -- and more likely, as based on clinical studies -- interferon alpha may directly attack the cancerous cells. Interferon alpha is primarily used to treat hairy cell and chronic myelogenous leukemias. Interleukin-2 has been an effective treatment for metastatic renal cell carcinoma. Although it is not certain exactly by which mechanism the drug acts, it is likely that it works to stimulate the immune system to attack the malignant cells. IL-2 therapy has been shown to increase the number of cytotoxic T-cells and natural killer cells (cells involved in immune response) in the body's circulation.
A problem with hormone therapy is that it works only temporarily: most tumors will eventually become resistant. The use of intermittent hormone therapy is currently under investigation for its benefits in reducing the cancer's resistance. Instead of treating a patient with antihormones continuously for the rest of the patient's life, they are only used in short bursts.
McKinnell, Robert, et al. The Biological Basis of Cancer. Cambridge: Cambridge UP, 1998.