Integrin Targeted Therapy for the Treatment of Ovarian Cancer

Applied Integrin Sciences, Inc., Los Angeles CA

Investigators

Linked publications, trials & patents

Abstract

Although prevention and early detection are the ultimate goals, the fact remains that 21,990 women in 2011 will be diagnosed with ovarian cancer in the U.S. Of these women 75% will be confronted with a high stage tumor and a five-year survival rate of 28%, which cannot be ignored. For these patients, improved treatment strategies for residual disease following surgery will aid in the reduction of complications during therapy as well as decrease the risk of cancer recurrence, which in turn would reduce mortality and improve the quality of life significantly. Given that ovarian cancer is predominantly confined to the peritoneal cavity, the strategy of localized intraperitoneal (IP) chemotherapy is highly desirable. Site-specific treatment results in tumor exposure of up to a 1000-fold increase in drug levels compared to what is possible with systemic delivery while reducing systemic toxicity. Especially in patients with minimal tumor burden after surgical debulking, regimens of IP chemotherapy are effective and lead to an increased progression-free and overall survival, but are accompanied with many side effects that are unacceptable to patients. In this study, it is proposed to use animal models of OC to evaluate IP treatment of early stage OC, mimicking disease recurrence, using the novel anti-invasive and anti-angiogenic disintegrin vicrostatin (VCN), a recombinant protein, impregnated in a carboxymethyl cellulose (CMC) and polyethylene oxide (PEO) gel approved for human use in Europe and Australia for prevention of post-surgical adhesions. This approach combines the benefits of high-concentration local peritoneal treatment as well as sustained drug delivery. Additionally, the CMC-PEO gel has the added benefit of preventing/reducing formation of post-surgical adhesions, a significant source of morbidity and therefore an important consideration in the management of ovarian cancer. Research goal: Using mouse models of ovarian cancer, the project will investigate the local and sustained effect of VCN delivered via a CMC-PEO gel on ovarian cancer growth and progression. In the initial studies we will determine the optimal formulation and ratios of CMC-PEO gel and VCN for maximizing the duration and level of VCN release under in vitro conditions. The CMC-PEO gel as a delivery vehicle is unique for several reasons: the viscous gel has the ability to hold VCN in suspension and slowly release it over time. This sustained slow release allows for maximization of the time the residual tumor is exposed to pharmacologic concentrations of the drug. Further, VCN diffusion from CMC-PEO gel provides for a continuous anti-tumor and anti-angiogenic affect. This proposed research has the capacity to make a significant impact in the management of ovarian cancer via treating residual disease and thereby decreasing mortality and increasing survival. Further, this translational research has the capability of impacting the morbidity associated with ovarian cancer by preventing the formation of post-surgical adhesions.