Project Summary (BDL) The Biomarker Development Laboratory (BDL) of the proposed BCC is proposed to discover, verify, prioritize, and validate biomarkers, and then to harness the power of selected multimodal biomarkers in the form of in vitro diagnostic multivariate index assays (IVDMIAs) for the early detection of high-grade serous ovarian carcinoma (HGSOC). Our proposed research strategy is guided by the working hypothesis that biomarkers that are biologically involved in or associated with precursor lesions or early HGSOCs are more likely to be able to capture HGSOC in women at a stage when cure may still be possible. This BDL proposal will primarily focus on HGSOC and its precursor, serous tubal intraepithelial carcinoma (STIC), because it is the most common type of ovarian cancer. This study is unique as we focus on identifying and studying biomarkers directly linked to early ovarian cancer and precursor tissues. Those early biomarkers are prerequisites for early detection of ovarian cancer to become a reality using Pap smear-based and blood-based samples. The aims are: 1. Continuation of current biomarker development pipeline 2. De novo biomarker discovery driven by the biology of HGSOC pathogenesis and early development and adherence to statistically principled methods. 3. (co-aim with BRL) Translation of discoveries into clinical tests – development of in vitro diagnostic multivariate index assays (IVDMIAs). 4. Development and evaluation of the falloposcope to detect HGSOC precursor lesions using BDL identified biomarkers. 5. Participation in EDRN network research projects. This proposed BDL, with its focused collections of clinical specimens from high-risk women, innovative approaches in study design, bioinformatics analysis, pathology support, and technology development, represents a unique yet highly promising endeavor to discover and validate biomarkers to capture HGSOC at precursor lesion and/or early curable stages. Our expected results will have significant impact on saving many women’s lives through early detection followed by surgical interventions.