Although most patients respond favorably to first-line chemotherapy, ovarian cancer remains the most lethal gynecological cancer in the United States primarily because of a high incidence of disease recurrence. The inability of traditional chemotherapy to eradicate tumor-initiating cells (TICs) is a plausible explanation for tumor relapse and we have begun to characterize TIC populations in ovarian cancer cell lines. Importantly, we are investigating the role of the NF-κB pathway in regulating this system. We have identified conditions that sustain a highly tumorigenic TIC population. Preliminary data suggest that NF-κB promotes and sustains TICs in ovarian cancer and current efforts are underway to characterize the molecular mechanisms underlying this preference. We will correlate activity of this pathway with expression of ovarian TIC protein markers such as CD133, Sox2, Nanog, and Oct-4 in TIC cell cultures and xenografts. Moreover we will use TICs to investigate effects of inhibiting this pathway on marker expression, proliferation, resistance to chemotherapy, and the ability to form tumors in mice. Clarifying the specific role of the NF-κB network in TIC populations will further our understanding of ovarian cancer initiation, progression, and relapse and may lead to improved therapeutic strategies for women in first remission, to prevent subsequent relapse to incurable disease.

Citation Format: Carrie D. House, Christina M. Annunziata. NF-κB signaling supports a sub-population of ovarian cancer tumor-initiating cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1923. doi:10.1158/1538-7445.AM2014-1923