Alkylating agents are compounds that work by adding an alkyl group to the guanine base of the DNA molecule, preventing the strands of the double helix from linking as they should. This causes breakage of the DNA strands, affecting the ability of the cancer cell to multiply. Eventually, the cancer cell dies. Alkylating agents were one of the first classes of drugs to be used against cancer. There are five traditional categories of alkylating agents:
- Nitrogen mustards (eg, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan)
- Nitrosoureas (eg, carmustine, lomustine, streptozocin)
- Alkyl sulfonates (eg, busulfan)
- Triazines (eg, dacarbazine, temozolomide)
- Ethylenimines (eg, altretamine, thiotepa)
Trabectedin is classed as a tetrahydroisoquinoline alkaloid, and unlike traditional alkylating agents, it binds to the minor groove of DNA and alkylates guanine at the N2 position. Alkylating agents are effective during every phase of the life cycle of a cancer cell, which means they are effective for treating a wide range of cancers. They are most effective for treating slow-growing cancers such as leukemia and solid tumors, but are also used in the treatment of breast, lung, ovarian, and prostate cancers; lymphomas, myelomas, and sarcomas; and Hodgkin's disease. Because alkylating agents affect all cells that are dividing frequently, they are also toxic to normal cells, particularly those of the gastrointestinal tract, bone marrow, testicles, and ovaries. Note: Although the platinum-containing anticancer agents, carboplatin, cisplatin, and oxaliplatin are frequently classified as alkylating agents, they are not. They cause covalent DNA adducts by another means.
