Nitrosoureas

Introduction

Nitrosoureas are a class of chemotherapy drugs that are used primarily in the treatment of certain types of cancer. They are known for their ability to cross the blood-brain barrier, making them particularly useful in treating brain tumors. Nitrosoureas are alkylating agents, which means they work by adding an alkyl group to the DNA of cancer cells, thereby interfering with their ability to replicate and ultimately leading to cell death.

Mechanism of Action

Nitrosoureas exert their cytotoxic effects through alkylation of DNA. They are unique among alkylating agents because they can cross-link DNA strands, which prevents DNA replication and transcription. This cross-linking is achieved through the formation of interstrand cross-links between guanine bases on opposite DNA strands. Additionally, nitrosoureas can carbamoylate proteins, which can inhibit DNA repair enzymes and further enhance their cytotoxicity.

Pharmacokinetics

One of the distinguishing features of nitrosoureas is their lipophilicity, which allows them to penetrate the blood-brain barrier. This property makes them effective in treating central nervous system malignancies. Nitrosoureas are typically administered intravenously, and they undergo spontaneous decomposition in the body to form active metabolites that exert their therapeutic effects.

Clinical Uses

Nitrosoureas are used in the treatment of various cancers, including:

• Glioblastoma multiforme and other brain tumors
• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Melanoma

Some of the commonly used nitrosoureas include:

• Carmustine (BCNU)
• Lomustine (CCNU)
• Streptozocin

Side Effects

The use of nitrosoureas is associated with several side effects, which can include:

• Myelosuppression, leading to decreased production of blood cells
• Nausea and vomiting
• Pulmonary toxicity, particularly with high doses of carmustine
• Nephrotoxicity, especially with streptozocin

Resistance

Cancer cells can develop resistance to nitrosoureas through various mechanisms, such as increased repair of DNA cross-links, increased drug efflux, and alterations in drug targets. Understanding these mechanisms is crucial for developing strategies to overcome resistance and improve treatment outcomes.

Also see

• Alkylating agent
• Chemotherapy
• Blood-brain barrier
• Cancer treatment

External links

• [Link to a reputable medical website about nitrosoureas]