Notch as a Diagnostic Marker and Therapeutic Target in Human Breast Cancer

Abstract

Abstract : We hypothesize that Notch and Jagged-1 expression on breast cancer cells, as well as Delta like-4 on breast tumor vessels, present a diagnostic and therapeutic target for detection and treatment of this devastating disease. Our combined objective is to utilize mouse models to establish whether 1) human breast cancer cells that express Jagged-1 and tumor vessels that express Delta-4, respectively can be detected using a novel diagnostic platform, 2) tumor derived proteins that shed upon Notch activation can be detected in serum of tumor bearing animals, and 3) blockade of Notch pathway activation, using neutralizing antibodies and a decoy receptor, will mitigate the growth of breast tumor in animals. The ultimate goal of these studies is to utilize the expertise of Drs. Diacovo and Kitajewski to validate Notch as a diagnostic and therapeutic target in breast cancer in order to develop paradigms that can be used in the clinic to detect and treat breast cancer.