Alkylating agents.
July 9, 2009 5:15 am Alkylating agents
Alkylating agents are the oldest class of anticancer drugs. Almost all of these drugs are active or latent nitrogen mustards. Nitrogen mustards are various poisonous compounds originally developed for military use. Alkylating agents all share a common mechanism of action, but differ in their clinical activity. They work by attacking the negatively charged sites on the DNA (oxygen, nitrogen, phosphorous and sulfur atoms). By binding to the DNA, steps (replication, transcription, and base pairing) leading to duplication of the cell’s genetic material are significantly altered. In addition, alkylation of DNA leads to DNA strand breaks and DNA strand cross-linking. By altering DNA in this manner, cellular activity is stopped and the cell dies. Chemotherapy drugs in this class are active in every phase of the cell cycle. As a result, this class of anticancer drugs is very powerful and is used in many types of cancer, including both solid tumors and leukemias.
In general, prolonged use of these drugs will lead decreased sperm production, cessation of menstruation, and possibly cause permanent infertility. This class of chemotherapeutics should never be used in the first trimester of pregnancy as they have been shown to increase fetal malformations. Use in the second or third trimester does not seem to carry the same risk. All alkylating agents can cause secondary cancers although not all agents are equal in their carcinogenic potential. The most common secondary cancer is a type of leukemia (AML, or Acute Myeloid Leukemia) that can occur years after therapy with an alkylating agent.