Novel Synthetic Hunter-Killer Peptides Target and Destroy Prostate Cancer

Abstract : Prostate cancer is now the most common cancer and the second most common cause of death from cancer, among men in the United States. Angiogenesis is required for prostate tumor survival, growth, and metastasis. We proposed to design and synthesize novel Hunter-Killer Peptides (HKPs), each representing a hybrid of an angiogenesis-targeting peptide and a mitochondrial membrane-disrupting peptide. While made to be non-toxic in the circulation, the HKPs will be preferentially toxic to mitochondria once internalized into angiogenic cells, via the targeting domain. We report here and in Ellerby et al., Nature Medicine, 5, 1032-1038, 1999, that while our prototypes contain only 21 and 26 amino acid residues, they are selectively toxic to angiogenic endothelial cells and show strong anti-cancer activity in mice (breast carcinoma xenografts). Work is underway to evaluate the HKPs for efficacy and toxicity 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.