Alkylating antineoplastic agent
Class of chemotherapy drugs
Alkylating antineoplastic agents are a class of chemotherapy drugs that work by adding an alkyl group to the DNA of cancer cells. This process interferes with the cell's replication and transcription, ultimately leading to cell death. These agents are used in the treatment of various types of cancer, including leukemia, lymphoma, and solid tumors.
Mechanism of Action[edit | edit source]
Alkylating agents exert their effects by forming covalent bonds with the DNA molecule. The alkyl group attaches to the guanine base of DNA, leading to cross-linking of DNA strands, abnormal base pairing, or strand breaks. This damage prevents the cancer cells from dividing and proliferating, triggering apoptosis or programmed cell death.
Classification[edit | edit source]
Alkylating agents can be classified into several subgroups based on their chemical structure and mechanism of action:
- Nitrogen mustards: These include cyclophosphamide, ifosfamide, and chlorambucil. They are among the oldest and most widely used alkylating agents.
- Nitrosoureas: Examples include carmustine and lomustine. These agents can cross the blood-brain barrier, making them useful in treating brain tumors.
- Alkyl sulfonates: Busulfan is a well-known agent in this category, often used in bone marrow transplantation.
- Triazines: Dacarbazine and temozolomide are examples, with temozolomide being used for glioblastoma.
- Ethylenimines: Thiotepa is an example, used in some breast cancer treatments.
Clinical Use[edit | edit source]
Alkylating agents are used in the treatment of a wide range of cancers. They are often part of combination chemotherapy regimens, where they are used alongside other drugs to enhance therapeutic efficacy. The choice of agent and regimen depends on the type of cancer, its stage, and the patient's overall health.
Side Effects[edit | edit source]
The use of alkylating agents is associated with several side effects due to their impact on rapidly dividing cells. Common side effects include:
- Myelosuppression: A decrease in bone marrow activity, leading to reduced production of blood cells.
- Nausea and vomiting: Often managed with antiemetic medications.
- Alopecia: Hair loss, which is usually temporary.
- Infertility: Due to effects on reproductive cells.
- Secondary malignancies: There is a risk of developing a second cancer, such as acute myeloid leukemia, years after treatment.
Resistance[edit | edit source]
Cancer cells can develop resistance to alkylating agents through various mechanisms, such as increased repair of DNA damage, increased drug efflux, or changes in drug targets. Overcoming resistance is a significant challenge in cancer treatment.
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