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Using current primary literature, discuss the aromatase-inhibiting anticancer drugs - Essay Example

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Most of the development and use of these drugs have been for cancers of the breast, as well as a selection of other cancers, found to express aromatase enzyme activity. Aromatase synthesizes…
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Using current primary literature, discuss the aromatase-inhibiting anticancer drugs
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Download file to see previous pages The paper will, then, continue with a discussion of the molecular structures, binding methods, and corresponding effects of the aromatase inhibitors (AIs).
The structure, function and binding interactions of the aromatase enzyme are still being investigated. Aromatase is a rate limiting enzyme in estrogen biosynthesis (Hong et al. 2009). It belongs to the monooxygenase family (particularly, the cytochrome P450 family) of enzymes and catalyzes the biosynthesis of oestrogen (specifically, oestrone) from androstenedione, involving a unique sequence of three reactions that require O2 molecules to produce an aromatic ring structure within the oestrogen molecule. The binding fit of androstenedione to aromatase is tight because the aromatase enzyme is not one of the promiscuous enzymes — which have looser fits for the various substrate structures they bind (Waterman, 2009). To conduct reactions, aromatase requires a partner enzyme, NADPH-cytochrome P450 reductase (Hong et al. 2009). High levels of aromatase enzyme expression and correspond oestrogen in tissues play a key role in augmented tumor growth. Blocking this biosynthesis pathway is the rationale behind the development of AIs (Pant & Dutta, 2008).
The reason that most of the development and use of AI drugs have been for cancers of the breast is that most breast cancer cases have up to ten times the amount of oestrogen found in the average circulatory system. It is important to note that aromatase activity (and the formation of oestrone) is more pronounced in postmenopausal women, which is why most AIs are commonly used for postmenopausal women with breast cancer (Waterman, 2009). The aromatase enzyme has also been identified in endocrine tissues (such as ovary, uterus, prostate, and bone) and cancer associated with these tissues. Interestingly, the enzyme has also been found to be expressed in non-endocrine tissues, such as liver, lung, and colon cancers ...Download file to see next pagesRead More
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