Grant: Travel Awards - Institute Community Support

Triple negative breast cancer (TNBC) is an aggressive type of breast cancer, which can invade other vital organs of the patients, and as a result causes death. The mortality rate in patients with TNBC is twice as that of estrogen receptor positive breast tumors. Currently, chemotherapy is the only therapeutic option for these patients. Since there are no FDA approved medications to treat TNBC patients, it is essential to develop a new drug-targeted therapy for them. Interestingly, some studies showed that estrogen related receptors (ERRs) play a crucial role in breast cancer, and cause adverse clinical outcomes in TNBC patients. Despite intensive efforts, no endogenous ligands have been identified for ERRs so far. The discovery of ligands that bind these receptors will allow the manipulation of their pathway and may lead to novel strategies for the treatment of TNBC. My results demonstrate that the identification of two potential endogenous ligands of ERRs: 1) estradienolone (ED), a novel endogenous steroid in human pregnancy, which binds to ERRs and blocks ERRs' activity and 2) cholesterol, which binds and activates ERRs. My specific objectives are (i) to determine whether ED and cholesterol regulate cell growth, invasion and transcription of ERR target genes in TNBC cells in a dose dependent manner; (ii) to determine whether the effect of cholesterol or lovastatin (a drug known to reduce cholesterol levels) in TNBC is dependent on ERR, in vitro and in vivo. The results from the proposed research may be of crucial significance for the development of therapeutic strategies for the treatment of TNBC.