Resistance to chemotherapy is one of the leading causes of death from breast cancer. Our lab discovered that Adenomatous Polyposis Coli (APC) loss in breast cancer cells results in an elevation of tumor-initiating cells (TICs) and resistance to chemotherapy-induced apoptosis. Given that TICs are often most resistant to standard chemotherapeutic compounds, we sought to understand the mechanism responsible for APC-mediated TIC enhancement. Our hypothesis is that the molecular mechanism involved in chemotherapeutic resistance parallels that promoting the TICs. APC-mutant cells have amplified activation of signal transducer and activator of transcription 3 (STAT3). Interestingly, inhibition of STAT3 with a small molecule inhibitor A69 decreases the TIC population and restores drug sensitivity. Studies are ongoing in the laboratory to investigate other molecular signaling pathways involved in APC-mediated enhanced TIC population and therapy resistance. These data have begun to reveal the molecular mechanisms of APC loss in breast cancer that can guide future treatment plans to counteract chemotherapeutic resistance.

Note: This abstract was not presented at the meeting.

Citation Format: Anne Arnason, Monica VanKlompenberg, Jenifer R. Prosperi. APC regulation of breast cancer therapeutic resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1081. doi:10.1158/1538-7445.AM2017-1081