Development of Dual Acting Inhibitors for Breast Cancer
Abstract
Breast cancer is the most common malignancy in the United States. It is estimated that approximately 30-40% of all breast cancers are estrogen-dependent. Currently, the most common treatments use either antiestrogen or aromatase inhibitors. They are effective in 35-40% of advanced postmenopausal breast cancer patients. In estrogen-dependent breast cancer patients, the estrogen levels in breast cancer cells are 5-10 times higher than in plasma. One of the possibilities to explain this observation is in situ production of estrogens from precursor substrates in the breast cancer cells. One of the pathways for the in situ production of estrogen is the conversion of androgens to estrogens by the enzyme aromatase (aromatase pathway). Another pathway for the in situ formation of estrogen is through the conversion of estrogen sulfate to estrogen by the enzyme estrogen sulfates (estrogen sulfates pathway). It has been pointed out that the estrogen sulfates pathway is significant and produce 10 times more estrogen than through the aromatase pathway in breast cancer cells. In addition, estrogen sulfates is also responsible for the conversion of dehydroepiandrosterone sulfate to androst-5-ene-3%, 1 7t3-diol, another estrogenic steroid in the body. Thus, potent estrogen sulfates inhibitors are potential agents for the treatment of estrogen- dependent breast cancer. Preliminary studies demonstrated that estrogen sulfates inhibitor can block the growth of NMU-induced tumor in rat stimulated by estrogen sulfate. Thus the current approach is to design dual acting inhibitors that can not only block the estrogen sulfates pathway, but also act as antiestrogens. The proposed dual acting inhibitors will have advantage over the current drug treatments. The inhibitors will not only block the formation of estrogen, but also block the stimulatory effect of estrogen on cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA410197
Entities
People
- Pui-kai Li
Organizations
- Ohio State University