Circulating tumor DNA: a noninvasive biomarker for tracking ovarian cancer

Ovarian cancer is the fifth leading cause of cancer-related mortality in women worldwide. Despite the development of technologies over decades to improve the diagnosis and treatment of patients with ovarian cancer, the survival rate remains dismal, mainly because most patients are diagnosed at a late stage. Traditional treatment methods and biomarkers such as cancer antigen-125 as a cancer screening tool lack specificity and cannot offer personalized combinatorial therapy schemes. Circulating tumor DNA (ctDNA) is a promising biomarker for ovarian cancer and can be detected using a noninvasive liquid biopsy. A wide variety of ctDNA applications are being elucidated in multiple studies for tracking ovarian carcinoma during diagnostic and prognostic evaluations of patients and are being integrated into clinical trials to evaluate the disease. Furthermore, ctDNA analysis may be used in combination with multiple "omic" techniques to analyze proteins, epigenetics, RNA, nucleosomes, exosomes, and associated immune markers to promote early detection. However, several technical and biological hurdles impede the application of ctDNA analysis. Certain intrinsic features of ctDNA that may enhance its utility as a biomarker are problematic for its detection, including ctDNA lengths, copy number variations, and methylation. Before the development of ctDNA assays for integration in the clinic, such issues are required to be resolved since these assays have substantial potential as a test for cancer screening. This review focuses on studies concerning the potential clinical applications of ctDNA in ovarian cancer diagnosis and discusses our perspective on the clinical research aimed to treat this daunting form of cancer.