Lung cancer is the leading cause of cancer deaths worldwide and is caused by mutations in DNA that promote uncontrolled cell growth or inappropriate cell survival. Patients have few therapeutic options, and disease progression is inevitable, underscoring the critical need for the identification of new therapeutic approaches to treat this disease. Our laboratory is one of the first to investigate the role of the cell surface protein PROTOCADHERIN 7 (PCDH7) in lung cancer development. PCDH7 represents an attractive target for treating lung cancer for several reasons. PCDH7 is present at higher levels in lung cancer cells compared to normal lung epithelial cells and high PCDH7 levels correl...
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Lung cancer is the leading cause of cancer deaths worldwide and is caused by mutations in DNA that promote uncontrolled cell growth or inappropriate cell survival. Patients have few therapeutic options, and disease progression is inevitable, underscoring the critical need for the identification of new therapeutic approaches to treat this disease. Our laboratory is one of the first to investigate the role of the cell surface protein PROTOCADHERIN 7 (PCDH7) in lung cancer development. PCDH7 represents an attractive target for treating lung cancer for several reasons. PCDH7 is present at higher levels in lung cancer cells compared to normal lung epithelial cells and high PCDH7 levels correlates with poor overall survival of lung cancer patients. We demonstrated that elevating or reducing PCDH7 levels in human lung cancer cells strongly potentiates or inhibits their tumor-forming ability, respectively. Similarly, elevating PCDH7 using mouse models progresses lung tumor development, while knocking out PCDH7 in a well-established lung cancer mouse model significantly reduces lung tumor burden and prolongs survival. Finally, knockout of PCDH7 in healthy mice does not negatively impact normal development. PCDH7 was recently shown to promote brain metastasis, further supporting the importance of this protein in multiple aspects of tumor biology and providing additional rationale for therapeutic targeting of this receptor. We have been developing novel antibodies that inhibit PCDH7 and its downstream signaling pathways in human lung cancer cells. The goals of this proposal are to fully characterize these antibodies directed against PCDH7, develop a humanized PCDH7 blocking antibody as a lung cancer therapy, and initiate preclinical development of the lead PCDH7 antibody. These studies will set the stage for development of individualized treatment based on targeting PCDH7 in lung cancer and other tumor types with high PCDH7 expression.
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