Cytotoxic Chemotherapy

Cancer is characterized by genetic mutations that inhibit or eliminate the normal controls on cell division. Many of today's non-surgical cancer treatments employ cytotoxic modalities that kill cancer cells or slows their replication by interfering with the apparatus of cell division. Cytotoxic chemotherapies focus on three strategies to inhibit cell division or induce apoptosis:

    1. Block the formation of the DNA building blocks, deoxyribonucleotides: guanine, adenine, cytosine, thymine.
    2. Alter DNA structure by strand breaks, mismatched base pairing or enzyme malfunctions which inhibit DNA and RNA synthesis
    3. Inhibit mitotic spindles functions required to separate chromosomes during mitosis.

Alkylating agents (AA) "Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA."

Three types of DNA damage have been associated with AA therapy:

  1. AN AA binds to DNA bases (guanine, adenine, cytosine) altering the configuration of the DNA strand. The intracellular enzymes that normally repair DNA errors are stabilized at the alkyl molecule causing fragmentation of the DNA strand.
  2. AN AA binds to DNA bases creating a cross link that prohibits strand separation required for DNA synthesis or transcription.
  3. An AA bond creates a conformational change that leads to deletion or mismatch in base pairing (mutation).

There are five groups of alkylating agents:

Plant alkaloids are a class of cell cycle specific cytotoxic agents derived from plant materials. They can be divided into 4 groups:

Anti-tumor antibiotics attack cancer cells by multiple mechanisms:

Antimetabolites are biochemical imposters that compete with the physiologic molecules necessary for normal cell function and replication. They often act by damaging DNA or impeding normal DNA synthesis or transcription.