Biomarkers and strategies for early detection of ovarian cancer

Abstract

Early detection of ovarian cancer remains an important unmet medical need. Effective screening could reduce mortality by 10%- 30%. Used individually, neither serum CA125 nor transvaginal sonography (TVS) is sufficiently sensitive or specific. Two-stage strategies have proven more effective, where a significant rise above a woman's baseline CA125 prompts TVS and an abnormal sonogram prompts surgery. Two major screening trials have documented that this strategy has adequate specificity, but sensitivity for early-stage (I-II) disease must improve to have a greater impact on mortality. To improve the first stage, different panels of protein biomarkers have detected cases missed by CA125. Autoantibodies against TP53 have detected 20% of early-stage ovarian cancers 8 months before elevation of CA125 and 22 months before clinical diagnosis. Panels of autoantibodies and antigen- autoantibody complexes are being evaluated with the goal of detecting >90% of early-stage ovarian cancers, alone or in combination with CA125, while maintaining 98% specificity in control subjects. Other biomarkers, including micro-RNAs, ctDNA, methylated DNA, and combinations of ctDNA alterations, are being tested to provide an optimal first-stage test. New technologies are also being developed with greater sensitivity than TVS to image small volumes of tumor.