Recent Patents on Biomarkers 2011, 1, 1-9 1 2210-3090/11 $100.00+.00 © 2011 Bentham Science Publishers Ltd. Patented Biomarkers for the Early Detection of Ovarian Cancer Roberta Veneroni $ , Claudia Peracchio $ , Roberta Castino and Ciro Isidoro* Laboratorio di Patologia Molecolare, Dipartimento di Scienze Mediche, Università del Piemonte Orientale A. Avogadro, 28100 Novara, Italy Received: November 22, 2010; Accepted: December 10, 2010; Revised: December 20, 2010 Abstract: Ovarian cancer is responsible for the highest fatality rate among the gynecologic malignancies, and there is a great urgency in defining screening tests for its early detection. Presently, CA125 is the only serum marker recommended for early detection (in combination with transvaginal ultrasonography) in hereditary syndromes and for differential diagnosis in suspicious pelvic mass. However, given the complexity of the pathogenesis and of the tumor-host interaction, it is unlikely that a single serum biomarker bears sufficient information for the specific discrimination of ovarian cancer at its very early stage form other non-malignant pelvic lesions. Consistently, CA125 has demonstrated its utility for monitoring the therapy and prognosis, but owing to its scarce sensitivity and specificity it is not recommended for screening of ovarian cancer in asymptomatic patients. Recently, the introduction of high-throughput multiplex tech- nologies, that allow to measure simultaneously a large number of molecules in the femtomolar range of concentration in the serum, has led to the definition of panels of biomarkers for the early detection of ovarian cancer. Here, we review the latest patents in this field. Keywords: Cancer biomarker, diagnosis, oncogenes, oncosuppressors, ovarian cancer, protein profiling. INTRODUCTION Ovarian Cancer 1: The Dimension of the Problem Each year more than 200.000 women are diagnosed with ovarian cancer worldwide. Statistics predict that 1 out 70 women will be diagnosed with ovarian cancer at some point during her life time [1]. Despite its relatively low incidence, ovarian cancer is an extremely lethal disease, ranking as the fourth to seventh leading cause of cancer-related deaths among women, depending on the geographical region considered. In 2010, the incidence of ovarian cancer in the United States was estimated around 22.000 new cases with approximately 14.000 deaths [2]. The high mortality ratio in ovarian cancer patients is primarily due to difficulties in diagnosing the disease at the very early stage, when symptoms are vague and aspecific. The 5 years survival rate in patients diagnosed with stage I ovarian cancer is >90%. Once the disease has metastasized to the pelvic organs (stage II), the abdomen (stage III) or beyond the peritoneal cavity (stage IV), the cure rate with current available therapy decreases substantially. However, only 20% of cases are diagnosed at stage I, while ~80 % patients present with stage III/IV tumors, for which the 5 years survival rate drops to 30%. The lack of specific clinical symptoms in the early phases of cancer development is the primary cause of late diagnosis. At stage I the tumor is confined to the ovary and unlikely would be noticed without the aid of a sensitive screening test. This justifies the *Address correspondence to this author at the Laboratorio di Patologia Molecolare, Dipartimento di Scienze Mediche, Università del Piemonte Orientale “A. Avogadro”, Via Solaroli 17, 28100 Novara Italy; Tel. ++39-0321-660607; Fax: ++39-0321-620421; E-mail: isidoro@med.unipmn.it $ These authors equally contributed to the work. nickname of “silent killer” attributed to ovarian cancer [3, 4]. In addition to late diagnosis, the persistence of dormant, drug-resistant cancer cells limits the possibility to definitively cure this disease. Ovarian Cancer 2: Challenges for the Discovery of Early Detection Biomarkers The discovering of tumor markers allowing to detect early onset of cancerogenesis or to monitor the progression of the disease and to predict the response to a chemotherapy regimen would be of obvious utility for the management of cancer patients. Most important, these markers must be sufficiently sensitive to detect ovarian cancer at a very early stage and highly specific in order to unequivocally distin- guish between malignant and benign lesions in the pelvis. The intrinsic complexity of the pathology combined with the individual metabolic and immunologic response in each patient lead to a complex and unique set of proteins expres- sed within the tumor tissue and the surrounding environment. There exist an initial phase in which the ability of host homeostatic systems may compensate for the local altera- tions provoked by the tumor-host interaction, therefore resulting in masking the presence of the tumor. In the case of serous ovarian cancers, this phase can last up to four years [5] and is clinically silent, though discomfort and other aspecific symptoms may be present and ignored by the patient and/or the physician [6]. Eventually, the growth of the tumor and the host reaction cause alterations that impact on the general homeostasis leading to quantitative and qualitative modifications of body fluids that are, in principle, detectable. Likely, more than one parameter will be affected and each of these may differ from the physiologic range that vary between individuals, being the result of the ‘conflict’ between the intrinsic characteristics of the tumor (mass, rate