Enzyme aromatase uses several androgen substrates for the biosynthesis of estrogen, i.e.
conversion of androstenedione to estrone and testosterone to biologically potent estradiol. Aromatase
inhibitors (AIs) such as anastrozole, letrozole and exemestane have been established in standard endocrine
therapy of breast cancer, by interfering with estrogen signaling cascade. Steroid sulphatase
(STS) regulates the level of active oestrogens and androgens in human target organs and
steroidogenic tissues, which have a key role in hormone dependent breast cancers (HDBC). Sulfatase
is still under the exploration stage and is yet to emerge as a potential therapeutic target in
breast cancer. The discovery of estrone 3-O-sulfamate (EMATE), a highly potent irreversible STS
inhibitor, accelerated the development of potent steroidal and nonsteroidal STS inhibitors. Attempts
are also being made for the development of dual inhibitors of AI and STS, as an alternative approach
to overcome the acquired resistance. This review includes the molecular structures and biochemistry
of aromatase and sulphatase enzymes. The advances in the development of inhibitors of the two enzymes
have also been outlined.
Keywords: Aromatase, breast cancer, cytochrome P450, DASIs, estradiol, steroidal sulphatase.
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