XBP1 is a multitasking transcription factor that is a key component of the unfolded protein response (UPR).
XBP1 is a point of convergence between estrogen-dependent pathways and the UPR, but the molecular
mechanisms are not well defined. Our preliminary data shows CREB3L2 is an XBP1-regulated gene whose
expression is increased during conditions of UPR and estrogen stimulated growth of ER-positive breast cancer cell lines. Our goal is to examine whether it can be used as a novel prognostic tool for patient outcome. The main objective of the proposal is to evaluate the association between expression of CREB3L2 and clinical outcomes including overall survival and disease-free survival of breast cancer patients. We will determine the expression of CREB3L2 by immunohistochemistry in breast cancers. CREB3L2 expression will be correlated with clinical follow-up data in a panel of 666 invasive breast cancers.
The ability to develop individualized biomarkers that predict recurrence of breast cancer will have a huge impact in reducing breast cancer mortality. The ability to identify high risk patients at the time of diagnosis will allow the treating oncologist to deliver aggressive adjuvant therapy to such patients. Equally important, the ability to identify patients who are not at high risk will allow us to spare toxic effects of chemotherapy to our patients who are deemed low risk.The proposed research could lead to better approaches to predict an individual patient’s responsiveness to endocrine therapies and to the development of new strategies to improve the efficacy of endocrine therapies and increase overall survival.
