Thao Dang, MD

Thao Dang, MD

Notch3 signaling pathway in human epithelial tumors

The goal of our funded research is to study the Notch3 signaling pathway in human epithelial tumors, with a major interest in lung cancer. In particular, we seek to understand the relationship between Notch signaling and oncogenic processes such as apoptosis, differentiation and metastasis. We also explore how Notch signaling crosstalks with other growth factor pathways in oncogenesis. Our long term goal is to use this information for [1] the better characterization and understanding of clinical lung cancer syndromes, and [2] develop and test molecular-based rational treatment concepts against human lung carcinoma.

Recent data from our laboratory and others indicate that overexpression of Notch3 is observed in many epithelial tumors. Furthermore, Notch3 upregulates a number of anti-apoptosis pathways leading to enhanced cancer cell survival. Inhibition of Notch3 by pharmacological or genetic means results in growth arrest and/or tumor cell death. Our work has also demonstrated significant crosstalk between Notch3 and EGFR signaling. This observation suggests that targeting multiple pathways in addition to Notch would yield higher tumor cytotoxicity. As part of our translational goal, we focus on developing strategies, such as monoclonal antibodies or recombinant proteins, to target Notch signaling either alone or in combination with other targeted therapies in preclinical and potential clinical studies.