Development of Antibodies Against Novel Cell Surface Proteins In Hormone Refractory Prostate Cancer. Addendum

摘要

N-cadherin is a cell surface marker that is overexpressed in hormone refractory prostate cancer and targeting this protein either diagnostically or therapeutically may have clinical utility. We developed monoclonal antibodies against several ectodomains of N-cadherin that reduced proliferation, adhesion and invasion of prostate cancer cells in vitro. In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis, and at higher doses led to complete tumor regression. In addition, N-cadherin antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology, angiogenesis, and reduced both AKT activity and serum IL-8 secretion. These data demonstrate that N-cadherin is a significant cause of both prostate cancer metastasis and castration resistance and therapeutic targeting of this factor with monoclonal antibodies may have significant clinical benefit. For the final year of the grant, there has been an increased attempt to identify the mechanism of action of these antibodies and their effects on downstream signaling pathways.