Novel Synthetic Hunter-Killer Peptides Target and Destroy Prostate Cancer

摘要

Prostate cancer is now the most common cancer among men in the United States. Angiogenesis is required for prostate tumor survival, growth, and metastasis. We proposed to design novel Hunter-Killer Peptides (HKPs), each representing a chimeric peptide of an angiogenesis-targeting peptide and a mitochondrial membrane-disrupting peptide. While non- toxic in the circulation, the HKPs will be preferentially toxic to mitochondria once internalized into angiogenic cells, via the targeting domain. As we reported in Ellerby et al., Nature Medicine, 5, 1032-1038, 1999, our prototypes contain only 21 and 26 amino acid residues, are selectively toxic to angiogenic endothelial cells and show strong anti- cancer activity in mice (breast carcinoma xenografts) . In the work described here, we evaluated the HKPs for efficacy and toxicity in a xenograft model of human prostate carcinoma, and in the TRAMP (transgenic adenocarcinoma mouse prostate) model for prostate cancer. The central theme of this research is to develop and appraise this new chemotherapy with the goal of producing both a safer, and more effective, treatment of advanced prostate cancer.