anthracyclines

Anthracyclines are a class of chemotherapeutic agents with antibiotic origins, derived from Streptomyces bacteria. The best known members are doxorubicin, daunorubicin, epirubicin, and idarubicin, with other related compounds sometimes grouped with this class due to shared mechanisms. They are among the most widely used anticancer drugs and are employed in various solid tumors and hematologic malignancies.

The primary anticancer actions of anthracyclines involve intercalation into DNA, inhibition of topoisomerase II, and generation of reactive oxygen species. These mechanisms produce DNA damage, impair replication and transcription, and promote apoptosis. The drugs are active across a broad range of cancers and are frequently used in combination regimens.

Commonly treated cancers include breast cancer, leukemias, lymphomas, sarcomas, ovarian cancer, and small cell lung cancer. Administration is typically intravenous; several liposomal formulations exist that alter tissue distribution and can reduce certain toxicities.

Toxicity is a major consideration with anthracyclines. Cardiotoxicity is dose-dependent and cumulative, increasing the risk of dilated cardiomyopathy and heart failure, sometimes long after treatment. Other adverse effects include myelosuppression, mucositis, alopecia, nausea, and vomiting. Extravasation during administration can cause local tissue injury.

Mitigation strategies include limiting cumulative dose, using cardioprotective agents such as dexrazoxane in selected cases, and employing liposomal formulations to reduce cardiac exposure. Regular cardiac monitoring (for example, echocardiography) is often recommended. Pharmacokinetically, they are given IV, have wide tissue distribution, undergo hepatic metabolism with biliary excretion, and display multi-phase half-lives. Drug resistance may arise from reduced uptake or increased efflux by transporters like P-glycoprotein.