Abstract A59: Developing novel peptide inhibitors to chromosomal cohesion using mRNA display for nanodrug delivery in breast cancer therapy

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 19; no. 10_Supplement; p. A59
• Main Authors: McCullum, Elizabeth O., Pati, Debananda
• Format: Journal Article
• Language: English
• Published: 01.10.2010
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.DISP-10-A59

Abstract Several specific molecular networks mediate the cellular proliferation of tumorogenic cells. One signaling pathway of interest is the transition from metaphase to anaphase which is dependent on cleavage of the cohesin protein complex by separase, an endopeptidase. A normal transition allows the protein complex to form, sister chromatid cleavage and the onset of anaphase. However, failure to properly assemble or maintain the integrity of this complex results in the premature separation of chromatids (PCS), mitotic arrest and apoptosis in cultured cells. This research effort will focus on the identification of cohesin Rad21, a proapoptotic protein that is over-expressed in breast cancer cells, mimcs for the induction of apoptosis in the cohesin-disrupted tumors. Using mRNA display, Rad21 mimetopes will be selected to bind a SMC-1 target in the formation of standard cohesin complex assembly. The pool of isolated peptides will be further characterized for their specificity, induction of PCS, mitotic arrest and apopotosis both in vitro and in vivo. Finally, peptides will be conjugated to a RAFT-peptide scaffold drug delivery system to exclusively target rapidly proliferating breast tumor cells. The potential advantages provide an area of promising therapeutics for antitumor effects when coupled with chemotherapy at the point of early detection. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A59.