Circulating cell-free DNA and circulating tumor cells, the “liquid biopsies” in ovarian cancer

Abstract

Limited understanding of ovarian cancer (OC) genome portrait has hindered the therapeutic advances. The serial monitoring of tumor genotypes is becoming increasingly attainable with circulating cell-free DNA (cf-DNA) and circulating tumor cells (CTCs) emerging as “liquid biopsies”. They represent non-invasive biomarkers and are viable, as they can be isolated from human plasma, serum and other body fluids. Molecular characterization of circulating tumor DNA (ct-DNA) and CTCs offer unique potentials to better understand the biology of metastasis and resistance to therapies. The liquid biopsies may also give innovative insights into the process of rapid and accurate identification, resistant genetic alterations and a real time monitoring of treatment responses. In addition, liquid biopsies are shedding light on elucidating signal pathways involved in invasiveness and metastasis competence; but the detection and molecular characterization of ct-DNA and CTCs are still challenging, since they are rare, and the amount of available samples are very limited. This review will focus on the clinical potential of ct-DNA and CTCs in both the early and advanced diagnosis, prognosis, and in the identification of resistance mutations in OC.

The NF‐κB‐modulated miR‐19a‐3p enhances malignancy of human ovarian cancer cells through inhibition of IGFBP‐3 expression

“…Ovarian cancer is the most lethal gynecological malignancy and it is known as a “silent killer” due to the lack of symptoms until advanced stages (III/IV) . Application of advanced surgical techniques and chemotherapy have improved treatment outcome, however, the overall survival rate is far from satisfied and the development of new diagnosis and treatment is still in urgent need …”

“…1,2 Application of advanced surgical techniques and chemotherapy have improved treatment outcome, however, the overall survival rate is far from satisfied and the development of new diagnosis and treatment is still in urgent need. 3 MicroRNAs (miRNAs) are short noncoding single-stranded RNAs of 19 to 24 nt long that can regulate gene expression after transcription. Mature miRNA binds to the 3′-UTR region of its target mRNA imperfectly, leading to enhanced degradation of target mRNA, and thereby inhibition of protein translation.…”

Circulating Tumor Cells Enumerated by a Centrifugal Microfluidic Device as a Predictive Marker for Monitoring Ovarian Cancer Treatment: A Pilot Study

“…CTCs are considered a liquid biopsy and a non-invasive method for diagnosis and prognosis. Samples can be easily collected at multiple time-points throughout treatment, which allows real-time monitoring of treatment response and drug resistance for all metastatic cancers [36]. Moreover, CTC analysis enables the detection of multiple mutations within a single cell, which contributes to an improved understanding of tumor heterogeneity and clonal evolution to establish a potential connection between mutational status and pathway activation by combining CTC genomics and transcriptomics [37].…”

Current progress in the clinical use of circulating tumor cells as prognostic biomarkers

“…CTCs expressing certain genetic profiles have allowed for the early detection of ovarian cancer, and also can be useful in guiding treatment decisions. 73 Platinumbased chemotherapy appears to enrich mesenchymal-like CTCs, suggesting that these cells, which express PI3Kα and Twist, could serve as specific indicators of the risk of developing therapy resistance. 74 Furthermore, these CTCs may represent useful therapeutic targets; PI3K/ Akt/mTOR pathway inhibitors currently are being investigated in preclinical and ongoing clinical trials, and other inhibitors of this population of CTCs, such as metformin, may be useful as well.…”

“…Consequently, additional validation and standardization of the assays are essential prior to clinical implementation of liquid biopsy approaches. CTCs expressing certain genetic profiles have allowed for the early detection of ovarian cancer, and also can be useful in guiding treatment decisions . Platinum‐based chemotherapy appears to enrich mesenchymal‐like CTCs, suggesting that these cells, which express PI3Kα and Twist, could serve as specific indicators of the risk of developing therapy resistance .…”