Cancer Chemotherapy

The purpose of chemotherapy is to kill cancer cells. The efficacy of a anticancer drug is measured by the degree of cancer regression and disappearance after the drug is administered. There exist two survivability characteristics of cancer cells under chemotherapy. In one case, the higher the dose of a given drug, the lower the number of surviving cancer cells. In the other, there exists a threshold beyond which a higher dose of the drug does not further shrink the cancer cell population. The latter characteristic is exhibited by drugs which act primarily at only one phase of the cell cycle.

Anticancer drugs can be roughly divided into three categories: alkylating agents, antimetabolites, and derivatives of natural products. Alkylating agents work by the covalent bonding of alkyl groups to intracellular macromolecules. Cancer cell toxicity is due to the binding of these alkyl groups directly to DNA bases. This results in DNA damage in the form of single-strand breaks and cross-linkage and ultimately prevents the cell from reproduction. Because alkylating agents bond directly to DNA, their cytotoxicity is specific to the cell division cycle, and is independent of the schedule of administration. An antimetabolite is an anti-cancer drug which is an analog of a normal metabolite. By being mistaken for a normal metabolite during the synthesis of DNA, such a drug inhibits normal nucleotide formation and prevents normal cell division. Most antimetabolites are cell-cycle specific. Drug effects are dependent on the schedule of administration. All drugs in this category affect cells in the "S" phase of the cell cycle.

Anticancer drugs derived from plants, fungi, and bacteria do not have a single mechanism of action. For example, Anthracyclines have several mechanisms of action, namely DNA intercalation (sitting between double helix), single and double strand breaks in DNA, and binding to cell membranes without even being transported into the cell. Bleomycin causes DNA double-strand breaks through a complex sequence of reactions involving the binding of the bleomycin-ferrous complex to DNA and unwinding of the double helix. Vinca alkaloids, derived from the periwinkle plant, bind to the protein tubulin and inhibit polymerization to form microtubules, which are important cell structures required in the separation of chromosomes. Platinum-based heavy metal drugs exert a similar effect to the alkylating agents. Hydroxyurea, an analog of urea, acts by inhibiting ribonucleotide reductase.

As blood cells are constantly being manufactured in the bone marrow, these cells are typically susceptible to chemotherapeutic drugs which target the fast dividing cancer cells. A common side-effect of chemotherapy is thus a drop in peripheral blood cell counts. How soon these blood components can recover becomes a limiting factor in the treatment interval.

Anticancer drugs are typically associated with a lot of toxic side effects. It seems hard to find an anticancer drug which only targets cancer cells without hurting normally dividing cells. Fortunately, with advances in genetic and immunological technologies, safe and effective anticancer drugs are now within reach.

Tannock, Ian, Hill, Richard P., Morgan, J. (1998) The Basic Science of Oncology (3rd ed.). McGraw-Hill, New York.