Abstract 3196: Genetic and pharmacologic approaches to overcome epithelial to mesenchymal mediated chemoresistance in breast cancer

Abstract

Abstract Development of resistance to conventional chemotherapy remains a major barrier to effective treatment of breast cancer. We and others have recently demonstrated in breast and pancreatic cancer models that epithelial-mesenchymal transition (EMT) may not be a critical mediator of cancer metastasis, however, it contributes to cancer drug resistance (Fischer et al. Nature 2015; Zeng et al Nature 2015). Importantly, blocking EMT through miR-200 family abrogated chemoresistance, indicating potentials for clinical translation. Using our novel EMT lineage tracing system, we have performed both genetic (CRISPR/Cas9 mediated genome-wide targeted mutagenesis) and pharmacological (high-throughput small molecule libraries) screens, to identify potential candidates to overcome EMT-mediated chemoresistance in breast cancer metastasis. The identified molecules provide not only novel mechanistic insights but also attractive anti-metastatic strategies for breast cancer treatment and the design of future clinical trials. Citation Format: Michael J. Crowley, Nasser Altorki, Vivek Mittal, Dingcheng Gao. Genetic and pharmacologic approaches to overcome epithelial to mesenchymal mediated chemoresistance in breast cancer [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 3196. doi:10.1158/1538-7445.AM2017-3196