Identification of inhibitory peptides directed toward E6 and E7 HPV oncoproteins for the development of novel therapies for tumors induced by HPV

Abstract

Human papillomavirus (HPV) is a DNA virus that infects mucosae and epithelium of the skin. It is the etiologic agent of tumors in different anatomical sites, such as cervix, anus, penis, vagina, vulva and also head and neck cancers. Together, HPV accounts for 5% of all new cases of cancers diagnosed annually worldwide. Expression by HPV of oncoviral proteins E6 and E7 help drive cells into a malignant state while blocking apoptosis pathways. Phage Display technology allows the construction of large random peptide libraries in the capside of filamentous phage and selection of ligands to virtually any biological target. Thus, the aim of this project is to use Phage Display technology to identify inhibitory peptides specific for HPV oncoproteins E6 and E7. These peptides will then be validated by their capacity to prevent cell growth induced by HPV. Because E6 and E7 interact with multiple pathways, we will also evaluate which intracellular targets are affected by our most promising peptides. These inhibitory peptides toward E6 and E7 will then serve as important leads for the development of less invasive, less toxic and more specific therapies for HPV-induced tumors.