Biao He, PhD
University of California, San Francisco
Identification of Novel Wnt Signaling-Related Therapeutic Targets Against Bronchioalveolar Carcinoma
Only a subset of patients with BAC have shown a robust and durable response to Tarceva and Iressa, and these patients eventually develop acquired resistance. Dr. He is investigating an additional pathway, Wnt, that could work synergistically with approved targeted therapies for lung cancer. Dr. He hopes to develop novel therapies for patients with surgically unresectable or recurrent BAC, patients who would otherwise have few viable treatment options.
Several important Wnt pathway related regulators and therapeutic targets have been identified as a result of this project:EMX2: Results suggest that EMX2 may play important roles as a novel suppressor in human lung cancer including BAC. Moreover, preliminary data shows that EMX2 expression is significantly associated with improved overall survival and recurrence free survival in patients with lung adenocarcinoma, particularly in patients with stage I disease and BAC, suggesting that EMX2 may be a novel prognostic marker for lung cancer. Dr. He is currently validating this exciting clinical correlation by using a different and larger cohert, and investigating how EMX2 regulates the Wnt gene expressions and metastasis in lung cancer. Gli proteins: Gli transcription factors were found to be activated in lung cancer including BAC. After confirming the functional importance of the Gli proteins in lung cancer, Dr. He investigated targeted inhibition of those onco-proteins, and has identified several small molecules that interfere with the function of Gli proteins. These compounds suppress the proliferation of lung cancer cells with Gli activation in vitro and inhibit the tumor growth in vivo, suggesting a putative novel effective strategy as lung cancer therapeutics. His team is currently optimizing these hit compounds in order to obtain more potent inhibitors for preclinical studies.
Dr. He has shown positive progress in his work, and was awarded over $1.7 million to continue his studies and filing two patents. Dr. He received the Eileen Ludwig Award in Thoracic Oncology Research at UCSF in 2007, was promoted to Associate Professor at Department of Surgery in 2009, and became a full Member of the Developmental Therapeutics Program and Cancer Genetics Program of the UCSF Helen Diller Family Comprehensive Cancer Center in 2010.