There are currently no tools available for the early detection of ovarian cancer. While CA-125 and HE4 are well-characterized biomarkers in ovarian cancer, their clinical application is currently restricted to analysis of therapeutic efficacy and detection of disease relapse. Blood is the preferred tissue for biomarker screening because it can be sampled non-invasively and is presumably the final destination for proteins secreted and shed from cells and tissues; hence in principle, blood provides a common biological reservoir for discovery of biomarkers. Unfortunately, direct measure of the protein complement in serum is complicated by the fact that the constituent components span some 12 orders of magnitude, with the 6-20 most abundant proteins comprising the majority (85%-97%) of total protein mass. Given the ultimate goal of biomarker detection early in disease onset, it is reasonable to suspect that proteins secreted or shed from a tumor at the initial stages of development, and subsequently diluted in the circulating blood, will be present at vanishingly low concentration relative to proteins such as hemoglobin or albumin. In contrast, is it reasonable to speculate that cancer-specific markers will be present at higher concentrations in tissue-proximal fluids. We are applying DEEP SEQ mass spectrometry to interrogate the secretomes of malignant cells versus benign FT counterparts in two tissue-proximal systems: (1) our fallopian tube (FT)-derived ex-vivo cultures, and (2) tissue interstitial fluid (TIF) from fresh matched tissues. In addition to CA125 and HE4, we found proteins not previously described in ovarian cancer that are expressed and secreted by cancer cells. Some of these proteins represent mobile genetic elements that are typically silenced in normal cells but get reactivated and expressed during neoplastic transformation. Ongoing work is defining their translational utility and biologic activity.
Early Detection Research in the Drapkin Lab in collaboration with the Tina Brozman Foundation.