Activity-based probes (ABPs) for broad protein families will be used to identify novel protein targets and small molecule leads relevant to ovarian cancer. Because ovarian cancer is often asymptomatic during its early and most treatable stages, it is imperative to identify increasingly sensitive markers for this disease. Also, as treatment for ovarian cancer is highly invasive and often produces painful and debilitating side effects, there is a great need for the identification of novel drug targets, which may allow for the identification or creation of more effective and specific drugs to combat this disease. In Phase I of this project, ActivX Biosciences will apply its eXamine platform, which identifies active proteins in complex samples, to 10 human ovarian tumors and their matched normal tissues. Initially, ABPs for serine hydrolases and kinases will be used to detect proteins that display altered activities in the tumor samples relative to the normal samples. The ActivX bioinformatics platform will be used to acquire quantitative information about protein activities from the activity-based profiles. This bioinformatics platform will also link this data to known information from the clinical samples. In Phase II, at least 100 paired tumor and normal ovarian tissues will be analyzed for activity. The activity-based profiles of these specimens will be processed for information linking protein activity to clinical characteristics. Proteins exhibiting significant alterations in activity or linkage characteristics will be analyzed for their use as markers or drug targets for the diagnosis and treatment of ovarian cancer. The information gleaned from this study may be commercialized through partnerships and commercial agreements with pharmaceutical, biotechnology, and diagnostics companies. Such agreements typically contain license fees for the use of the technology in biomarker identification, drug-target identification, and cancer diagnostics, in addition to milestone and royalty payments.
