Aromatase, its inhibitors and their use in breast cancer treatment.
Aromatase, a cytochrome P450 enzyme, catalyses the rate-limiting step in the biosynthesis of estrogens. Many processes in male and female development and reproduction and especially in the growth of hormone-dependent cancers, are dependent on estrogens. Therefore, controlling estrogen production by inhibition of aromatase is a logical treatment strategy. Two classes of aromatase inhibitors, steroidal and non-steroidal compounds, are now coming into use. Among the steroid substrate analogs, 4-hydroxyandrostenedione has been shown to be effective in breast cancer patients with advanced disease and was recently approved for treatment in the United Kingdom. Several highly potent and selective non-steroidal inhibitors are now in clinical trials. The variety of compounds that act as aromatase inhibitors should provide breast cancer patients with a number of new treatment options.
Brodie
A M
AM
Department of Pharmacology, School of Medicine, University of Maryland, Baltimore 21201-1559.
D000616:Aminoglutethimide / Q000627:therapeutic use; D000735:Androstenedione / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001141:Aromatase / Q000502:physiology; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010293:Pargyline / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004967:Estrogens; D000616:Aminoglutethimide; D000735:Androstenedione; D010293:Pargyline; D001141:Aromatase; C033071:plomestane; C014594:formestane