Abstract IA05: Leveraging preclinical models of triple negative breast cancer for translational research

Abstract

Abstract We have developed multiple novel preclinical syngeneic triple negative breast cancer(TNBC) genetically engineered mouse (GEM) models, which have been characterized genomically and with respect to their immune microenvironments. By integrating the immunological characterization of murine syngeneic mammary tumor models with analyses of human breast cancer datasets, we have demonstrated a relationship between EMT and myeloid cells, specifically tumor-associated macrophages (TAMs). We also have leveraged our syngeneic GEM models to define the response to immune checkpoint blockade therapy (ICBT) with emphasis on the myeloid cell environment. We have used our GEM models to test single agent drugs along with standard-of-care therapies for appropriate durations. Finally, we have tested these treatment regimens on established metastases with sufficient tumor burdens. Specifically, we will present results illustrating how CSF-1R targeting therapy combined with metronomic chemotherapy enhances a B and T cell response for the treatment of metastatic TNBC. In additional we well discuss how targeting the RNA helicase eIF4A that unwinds the secondary structures in the 5’UTR of mRNAs to facilitate translation initiation triggers an interferon response to suppress TNBC. Citation Format: Jeffrey M Rosen, Diego Pedroza, Na Zhao, Xiang H-F Zhang, Charles M Perou. Leveraging preclinical models of triple negative breast cancer for translational research [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr IA05.