Apolipoprotein E: A novel therapeutic candidate for metastastic breast cancer

• Applicant: Privatdozent Dr. Benjamin Ostendorf, Ph.D.
• Subject Area: Hematology, Oncology
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 263265951

Most patients with solid tumors die of the spread of the primary tumor to distant organs. Considering breast cancer only, metastasis leads to more than 400 000 deaths per year. To date, effective therapies for metastatic breast cancer are lacking.Recently, the metabolic protein Apolipoprotein E (ApoE) was identified as a robust suppressor of metastasis in melanoma, a tumor sharing many biological features with breast cancer. Preliminary data revealed ApoE to suppress key pro-metastatic processes of several human breast cancer populations: invasion and endothelial recruitment. Treatment of breast cancer cells with ApoE also led to a reduction of metastasis in a mouse Xenograft model.This application aims at evaluating the efficacy of ApoE as a novel therapy for metastatic breast cancer. To this end, three challenges will be addressed:First, we will use a range of different breast cancer cell lines in Xenograft-, immunocompetent allograft- and in a genetically engineered mouse model of breast cancer to evaluate the ability of ApoE to inhibit metastasis.Second, the ability of ApoE to suppress metastasis will be tested on breast cancer cell lines that are resistant to conventional targeted therapies, such as the anti- estrogen Tamoxifen and the Her2-antibody Trastuzumab. To accomplish this aim both in vitro cell culture experiments and in vivo mouse models will be employed.Third, we will aim at identifying the receptor that mediates the anti-metastatic effects of ApoE. For this purpose we will use RNA interference to selectively silence each one of the known four ApoE-receptors. Accomplishing this aim will allow us to identify patients who will benefit from ApoE-directed therapy.This work is supposed to provide the basis for developing an ApoE-based therapy for human metastatic breast cancer as a novel and first-in-class therapeutic approach.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Sohail Tavazoie, Ph.D.