NOVEL AGENT TO RESTORE SENSITIVITY TO ANTI-ESTROGEN THERAPY

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Aromatase Inhibitors (AI) are the preferred hormonal treatment for estrogen receptor positive Breast Cancer (BC) in postmenopausal women and are used to treat approximately 140,000 patients annually in the US. However, ~40% of patients will be, or become resistant to AIs. If sensitivity to AI can be re-established in patients that have become resistant, this would be a major step forward in treating ER+ BC patients. The PI has characterized a growth factor, GP88, and demonstrated its critical role in the development, proliferation and survival of cancer cells. Importantly, the PI has demonstrated using in vitro studies that GP88 is a driver in controlling cancer cell resistance to AIs such as Letrozole. The PI has developed a neutralizing monoclonal anti-GP88 antibody, shown in vitro to return BC cell sensitivity to AIs in previously AI resistant cell lines. This application seeks to prove through the use of xenograft studies that anti-GP88 is effective in vivo in restoring AI sensitivity in previously resistant tumors. If successful, anti-GP88 in conjunction with AI therapy in AI resistant patients would be a major advancement in treating BC patients that currently have systemic chemotherapy as their only option and could improve overall BC survival.