Our current research program is focused on determining the role oxidative stress and related signaling pathways play in mediating the mechanism of action of potential anticancer agents. In particular, we evaluate potential drugs that target the aryl hydrocarbon receptor (AhR) signaling pathway to inhibit the growth of breast cancer including the estrogen receptor negative (ER-) subtype. ER- breast cancer occurs at a disproportionate frequency among African American patients. AhR is a ligand-activated transcription factor historically associated with mediating the metabolism and deleterious effects of certain procarcinogens. More recently, substances that activate AhR signaling have been shown to display chemopreventive effects. Our goal is to elucidate molecular mechanisms whereby AhR ligands promote their anticancer and/or chemopreventive actions within breast cancer cells. Such agents could especially benefit ER- breast cancer patients as no targeted agents currently exist for this subtype. We are particularly interested in the role that these potential agents may play in reactivating epigenetically silenced tumor suppressor genes within breast cancer cells and corresponding tumor tissues.
I am an affiliate member of CHDMM keenly interested in developing targeted agents to treat estrogen receptor-, progesterone receptor- and HER2/neu-negative (triple negative) breast cancer which occurs more frequently among women of African decent.
1. McLean, L., Soto, U., Agama K., Francis, J., Jimenez, R., Pommier, Y., Sowers, L., and Brantley, E. (2008) Aminoflavone induces oxidative DNA damage and reactive oxygen species-mediated apoptosis in breast cancer cells. Int. J. Cancer. 122 (7):1665-1674.
2. Brantley, E., Kohlhagen, G., Antony, S., Meng, LH., Agama K., Stinson, S.F., Sausville, E.A. and Pommier, Y. (2006) Anti-tumor drug candidate 2-(4-Aminophenyl)-5-fluorobenzothiazole induces single-strand breaks and DNA-protein cross-links in sensitive MCF-7 cells. Cancer Chemother Pharmacol. 58(1):62-72.
3. Brantley, E., Patel, V., Hose, C., Ciolino, H.P., Yeh, G.C., Trapani, V., Stinson, S.F., Sausville, E.A. and Loaiza-Perez, A.I. (2005) The antitumor drug candidate 2-(4-amino-3-methylphenyl)-5-Fluorobenzothiazole activates NF-kB signaling in MCF-7 cells in response to DNA damage. Anticancer Drugs. 16 (2):137-143.
4. Brantley, E., Trapani, V., Alley M.C., Hose, C.D., Bradshaw, T.D., Stevens, M.F.G.and Stinson, S.F. (2004) Fluorinated 2-(4-amino-3-methylphenyl)benzothiazoles are metabolized and bind to sub-cellular macromolecules in sensitive human cancer cells. Drug Metab Dispos. 32(12):1392-401.
5. Chua, M.-S., Kashiyama, E., Bradshaw, T.D., Stinson, S.F., Brantley, E., Sausville, E.A. and Stevens, M.F.G. (2000) Role of CYP1A1 in modulation of the antitumor properties of the novel agent 2-(4-Amino-3-methylphenyl) benzothiazole (DF 203, NSC 674495) in human breast cancer cells. Cancer Res. 60(18):5196-203.