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Folic acid is an essential vitamin in nutrition and performs a large variety of metabolic roles. Folate is a term that refers to compounds that are derived from folic acid, primarily by attaching folic acid to a larger molecule. The body converts folic acid to the folate coenzymes to perform its functions. In terms of cancer, the most important function of the folate coenzymes is in the synthesis of nucleic acids, which are components of the DNA molecule. DNA synthesis is essential for cells to grow and divide, and cancer cells have evolved a mechanism to capture folate more effectively than in normal cells. This knowledge has allowed cancer researchers to develop novel methods of cancer treatments.
Folate deficiency can lead to abnormal DNA synthesis resulting in chromosome breaks and disruption in DNA repair. Folate deficiency can also inhibit the expression of some genes. Although folic acid deficiency due to diet is quite rare, alcohol is a known antagonist, and alcohol consumption could possibly lead to deficient folate status in the body. A study by Zhang and associates 5 found that total folate intake was not associated with overall risk of breast cancer. However, among women who consumed alcohol, the risk of cancer was highest among those with low folate intake. These findings, therefore, suggest that folic acid supplementation for people that consume alcohol may be beneficial in some instances in preventing cancer. Antifolates as antitumor agents Recognizing the essentiality of folates to cancer growth and division, researchers have long worked on developing antifolates to inhibit cancer. Antifolates are compounds that are similar enough in structure to folic acid that they fool the cell into attempting to use them in metabolism. Typically, the antifolate inhibits a folate coenzyme by binding to it. Recently, a novel antifolate has been developed that is called pemetrexed. 2 This antifolate gains entry into the cell by binding to a folate carrier on the cell surface. Once inside the cell, pemetrexed can inhibit multiple enzyme systems. Clinical trials have shown that pemetrexed demonstrates activity against a wide variety of solid tumors, either singly or in combination with other drugs. Typical responses (inhibition of tumor growth) range between 15-30%, depending on the type of tumor. Why doesn't the antifolate drug does not interfere with folate metabolism in the normal cell as well, leading to folate deficiency? As it turns out, the cancer cell has a greater affinity for folates, leading to a much greater uptake of the antifolate in the cancer cell. The studies with pemetrexed, however, indicate that providing patients with folic acid supplements results in reduced toxicity to the drug, while maintaining antitumor activity. Go To Page: 1 2
The copyright of the article The Use of Folates in Cancer Therapy in Cancer Treatment is owned by . Permission to republish The Use of Folates in Cancer Therapy in print or online must be granted by the author in writing.
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