Development of a Multifaceted Ovarian Cancer Therapeutic and Imaging Agent

Abstract

Abstract : Ovarian cancer (OC) is the deadliest of all gynecological cancers, with five year survival rates of <45%. One critical feature of the disease is that two thirds of the women diagnosed have advanced disease, and the five year survival rate of this group is <30%. This project outlines the development of a recombinant version of a member of a class of proteins known as disintegrins as an innovative imaging and diagnostic agent for ovarian cancer (OC). Vicrostatin (VN) is a recombinant protein based on the venom disintegrin contortrostatin (CN), which has shown impressive antitumor and antiangiogenic activities in models of human ovarian cancer. OC cells have been shown to display integrins alphavbeta5 and alpha5beta1, and the antitumor activity of CN, and demonstrated for VN, is based on the high affinity interaction between the disintegrin and these integrins. Thus far we have developed and shown that we have a robust and viable system for the production of VN and that the protein produced displays a high affinity for integrins displayed on ovarian cancer cells. In ongoing experiments we are evaluating the imaging potential for VN to be used for both evaluation of treatment and diagnosis of OC. The high affinity of VN for the integrins found on OC cells make for an excellent candidate for improvement of OC diagnosis and therapy.