Abstract P6-01-08: Identifying metastatic drivers in patient derived xenograft models of triple negative breast cancer

Abstract

Abstract Metastases are responsible for the vast majority of deaths due to breast cancer. Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high rates of metastasis and poor response to chemotherapy. We are using patient derived xenograft (PDX) models of TNBC to identify drivers of TNBC metastasis. Using these models, we demonstrated that human breast tumors are capable of completing all stages of the metastatic cascade in mice, and metastatic lesions are observed in organs normally found in patients with metastatic breast cancer including lung, liver, bone, brain and lymph nodes. Lentiviral transduction was employed to express both bioluminescent and fluorescent proteins in three distinct PDX models of TNBC. In this way, metastatic lesions can be isolated using bioluminescent imaging and circulating tumor cells (CTCs) are isolated by flow cytometry. A lung metastasis gene expression signature was generated and comprehensive gain-of-function screens are being conducted in vivo to validate this signature and identify functional drivers of TNBC metastasis. Citation Format: Powell E, Shao J, Tieu T, Peoples M, Bristow C, Manyam G, Cai S, Tu Y, Edwards JR, Heffernan TP, Piwnica-Worms D, Liang H, Piwnica-Worms H. Identifying metastatic drivers in patient derived xenograft models of triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-01-08.