Title: Personalized Irinotecan Treatment: the patient matters
Abstract:textabstractIn the early sixties of the last century, camptothecin (CPT) was isolated from the Chinese
plant Camptotheca acuminata (Nyssaceae family), and was found to be a very potent
antitumor agent...textabstractIn the early sixties of the last century, camptothecin (CPT) was isolated from the Chinese
plant Camptotheca acuminata (Nyssaceae family), and was found to be a very potent
antitumor agent in vitro. However, its clinical development was hindered by a relatively
limited clinical activity and severe and unpredictable toxicities, most problematic being
hemorrhagic cystitis and enteritis. These turned out to be partially related to the poor
hydrophilicity of the drug and the initial administration of camptothecin in the inactive
carboxylate form. Once the mechanism of action of camptothecin was discovered,
there was renewed interest in the drug. Eff orts were made to develop water-soluble
camptothecin analogues with improved antitumor activity and decreased toxicity. Irinotecan,
also known as CPT-11, was developed as a water-soluble prodrug of SN-38, a very
potent camptothecin analogue, which has a 100-1000 fold higher cytotoxic activity
in vitro than the parent compound. Camptothecins, including irinotecan and SN-38,
inhibit the enzyme topoisomerase-I by binding to it and forming a stable complex
between topoisomerase-I and DNA. This induces single-strand breaks in chromosomal
DNA, ultimately leading to cytotoxicity and apoptosis.Read More
Publication Year: 2011
Publication Date: 2011-06-17
Language: en
Type: article
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