Targeting STAT1 signaling for therapeutics against metastatic breast cancer

Breast cancer remains a common cancer and significant public health problem, with over 232,240 new cases annually in the United States. In 2013, it is estimated that about 40,000 people will die from breast cancer, with 5-year survival decreasing dramatically from stage I disease (over 90%) to stage III disease (57%). Patients with the stage III or above breast cancer generally die from cancer metastasis. Thus, it is critical that we develop clinically applicable assays or diagnostic assays that are predictive of metastasis risk. We have recently identified that STAT1 signaling plays an important role in breast cancer progression. STAT1 overexpression in invasive cancer cells leads to increased expression of inflammatory cytokines that recruits immune suppressive cells. These immune suppressive cells function to avoid immune detection and eradication of tumor cells, leading to aggressive tumor progression. In this application, we propose to perform a retrospective study to determine whether STAT1 and STAT1-regulated cytokine expression levels are indicative of metastasis risk in breast cancer specimens. We will also analyze gene expression of STAT1 and key STAT1-regulated cytokines in breast cancer specimens before and after chemotherapy and determine whether chemo-resistant tumors have enhanced expression levels of STAT1 and cytokines. Finally, we will perform in vitro cell culture study to test FDA-approved inhibitors of STAT1 in invasive/metastatic breast cancer cells. The goal is to develop new anti-STAT1 treatments for metastatic breast cancer that can be quickly translated into clinical therapy.