The discovery and mechanism of action of letrozole.

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Bhatnagar AS

The discovery and mechanism of action of letrozole.

Breast Cancer Res Treat. 2007;105 Suppl 1:7-17. doi: 10.1007/s10549-007-9696-3. Epub 2007 Oct 3.

PubMed ID

17912633 [ View in PubMed

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Abstract

Because estrogen contributes to the promotion and progression of breast cancer, a greater understanding of the role of estrogen in breast cancer has led to therapeutic strategies targeting estrogen synthesis, the estrogen receptor, and intracellular signaling pathways. The enzyme aromatase catalyses the final step in estrogen biosynthesis and was identified as an attractive target for selective inhibition. Modern third-generation aromatase inhibitors (AIs) effectively block the production of estrogen without exerting effects on other steroidogenic pathways. The discovery of letrozole (Femara) achieved the goal of discovering a highly potent and totally selective AI. Letrozole has greater potency than other AIs, including anastrozole, exemestane, formestane, and aminoglutethimide. Moreover, letrozole produces near complete inhibition of aromatase in peripheral tissues and is associated with greater suppression of estrogen than is achieved with other AIs. The potent anti-tumor effects of letrozole were demonstrated in several animal models. Studies with MCF-7Ca xenografts successfully predicted that letrozole would be clinically superior to the previous gold standard tamoxifen and also indicated that it may be more effective than other AIs. An extensive program of randomized clinical trials has demonstrated the clinical benefits of letrozole across the spectrum of hormone-responsive breast cancer in postmenopausal women.

DrugBank Data that Cites this Article

Drugs

Letrozole

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Letrozole	Cytochrome P450 2A6	Protein	Humans	Unknown	Substrate Inhibitor	Details
Letrozole	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate	Details

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Letrozole	Serum albumin	Protein	Humans	Unknown	Binder	Details