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Between all of the gynecological cancers, ovarian cancer (OvCa) shows high clinical challenge because it is difficult to be detected in early stage and it has the highest mortality proportional to the other gynecologic malignancies. Despite medical advances and the development of diagnostic tools such as biomarkers and detection techniques, OvCa remains a fatal cancer with high progression. There are different types of OvCa based on histological classification; Epithelial Ovarian Cancer (EOC) is the most common, whereas, stromal and germ cell tumors are of lower abundance. EOC is identified in over 80% of women at late-stage with complications include the spread of tumor implants throughout the peritoneal cavity. Early diagnosis of OvCa is helpful in the treatment and promotion of survival rate. Such diagnostic medical methods and biomarkers include vaginal and pelvic examination, diagnostic imaging, serum CA125, and screening tests or a combination used in medical centers, however, it is necessary to find new biomarkers with long-term stability and high specificity and sensitivity to detect OvCa in early stages of disease. This review presents novel and robust biomarkers and methods for detecting OvCa.