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• W2004685736 endingPage "344" @default.
• W2004685736 startingPage "333" @default.
• W2004685736 abstract "Estrogens are involved in numerous physiologic processes and have crucial roles in particular disease states, such as mammary carcinomas. Estradiol, the most potent endogenous estrogen, is biosynthesized from androgens by the cytochrome P-450 enzyme complex called aromatase. Aromatase is found in breast tissue, and the importance of intratumoral aromatase and local estrogen production is being unraveled. Inhibition of aromatase is an important approach for reducing growth stimulatory effects of estrogens in hormone-dependent breast cancer. Effective aromatase inhibitors have been developed as therapeutic agents for controlling estrogen-dependent breast cancer. Investigations into the development of aromatase inhibitors began in the 1970s and have expanded greatly in the past three decades. Competitive aromatase inhibitors are molecules that compete with the substrate androstenedione for noncovalent binding to the active site of the enzyme to decrease the amount of product formed. Steroidal inhibitors that have been developed to date build on the basic androstenedione nucleus and incorporate chemical substituents at varying positions on the steroid. The structure–activity relationships for steroidal inhibitors have become more refined in the past decade, and only some modifications can be made to the steroid and still keep its affinity for aromatase. Nonsteroidal aromatase inhibitors can be divided into three classes: aminoglutethimide-like molecules, imidazole/triazole derivatives, and flavonoid analogs. Mechanism-based aromatase inhibitors are inhibitors that mimic the substrate, are converted by the enzyme to a reactive intermediate, and result in the inactivation of aromatase. Aromatase inhibitors, both steroidal and nonsteroidal, have shown clinical efficacy for the treatment of breast cancer. The initial nonselective nature of nonsteroidal inhibitors such as aminoglutethimide has been greatly reduced in the later generations of inhibitors, anastrozole and letrozole. Mechanism-based steroidal inhibitors such as 4-hydroxyandrostenedione and exemestane produce prolonged aromatase inhibition in patients. The potent and selective third-generation aromatase inhibitors anastrozole, letrozole, and exemestane are approved for clinical use as second-line endocrine therapy in postmenopausal patients failing antiestrogen therapy alone or multiple hormonal therapies." @default.
• W2004685736 created "2016-06-24" @default.
• W2004685736 creator A5071290232 @default.
• W2004685736 date "2001-09-01" @default.
• W2004685736 modified "2023-10-18" @default.
• W2004685736 title "Aromatase, Aromatase Inhibitors, and Breast Cancer" @default.
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