A second method of classification involves grouping by the mechanism of action – how the drug of choice works. The two main ways in which anti-cancer drugs work is through inhibition or disruption of normal DNA functions.
Angiogenesis Inhibitors
Cancer tumor cells require additional blood supply. Angiogenesis is the process by which cancer cells form new blood vessels to support tumor growth. These blood vessels also facilitate the spread of cancer cells (metastases). Inhibiting angiogenesis “starves” the tumor cells leading apoptosis or senescence and may limits the spread of cancer cells to surrounding areas. Thalidomide, associated with severe birth defects, is now being considered for anti-cancer use because of its angiogenesis inhibiting properties. Other drugs used include Endostatin, Fumagillin, Genestein, and Monocycline, etc.
DNA Intercalators/Cross-linkers
Intercalation refers to the act of inserting a DNA altering substance. Cross-linking involves building a connection (link) between gene strands. Either process is intended to alter the DNA structure of a tumor cell to disrupt its function. Carboplatin and Oxyplatin form cytotoxic adducts with DNA and induces apoptosis. Bleomycin inhibits DNA synthesis, induces breaks in base DNA sequences, and inhibits tumor angiogenesis. Other drugs in this group include Carmustine, Chlorambucil, and Cyclophosphamide.
DNA Synthesis Inhibitors
Synthesis is the process by which cancer cells split and proliferate. Synthesis inhibitors, as the name suggests, are more active in the S phase of the cell cycle. These drugs bind to specific DNA types to block production of enzymes needed for cell synthesis. For example, Menthtrexate and Aminopterin are folic acid antagonists which block thymidine biosynthesis by which cells in S phase are synchronized. Other drugs in this class work similarly to inhibit production different enzymes also affecting synthesis.
DNA-RNA Transcription Regulators
During cell synthesis, the cell’s DNA template synthesizes messenger RNA to carry genetic information from the DNA molecule to new cells. This process is called transcription, a necessary function for cell replacement. Unfortunately, it works as well for tumor cells as it does for normal cells. DNA-RNA Transcription regulators attempt to block synthesis and or induce apoptosis in cancer cells by inhibiting or reversing production of RNA components. For example, Actinomycin D works by inhibiting cell proliferation and blocking production of mRNA by RNA polymerase to induce apoptosis.
Enzyme Inhibitors
Molecules that bind to enzymes and decrease their activity are called enzyme inhibitors. The following picture shows a representation of HIV protesase enzyme as red, blue and yellow ribbons with the bound protease inhibitor ritonavir as a stick-and-ball model in the center.
Different drugs bind to different enzymes to increase the specificity of drug choice. Enzyme inhibitor binding is either reversible or irreversible. Irreversible inhibitors change the chemical composition of the enzyme. Reversible inhibitors produce different types of inhibition depending upon whether it binds with the enzyme, the enzyme sub-strate complex, or both. In either case, the purpose is interrupt the enzyme activity resulting in apoptosis and/or interruption of synthesis and transcription.
Gene Regulation (therapeutic gene modulation)
This class of drugs alters the expression transcription, translation, and phenotypic manifestation) of a gene at one of the various stages. Most clinical research seems to be in the area of translation through RNA interference. Examples include Melatonin which inhibits proliferation of breast cancer cells by inhibiting estrogen receptor action and Tamoxifen, a selective estrogen response modifier used with estrogen-sensitive tumors.
Microtubule Inhibitors
Microtubules are cylindrical, hollow structures that support cell structure and facilitate cellular movement and transport. Tubulin, a globular protein, is the basic structural constituent of microtubules. Most drugs in this class function by binding to tubulin or β-tubulin to induce apoptosis or prevent cell division. Paclitaxel and Navelbine are two examples.
New drugs are appearing almost weekly, many with unique functions that do not easily fall into on of these classes.
For more information about specific drugs, visit Chemocare.com
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