Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA

Giannopoulou, Lydia; Kasimir‐Bauer, Sabine; Lianidou, Evi

doi:10.1515/cclm-2017-0019

Cited by 71 publications

(62 citation statements)

References 88 publications

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“…In addition, because the CA125 level may not change rapidly enough to reflect the effect of the treatment, ctDNA from plasma has been studied as a promising alternative [22,23]. Previous studies demonstrated that ctDNA in plasma from ovarian cancer is a prognostic biomarker and associated with the time to progression [24][25][26]. Using targeted next-generation sequencing of serial plasma ctDNA, we found that ctDNA from plasma detects ovarian cancer progression/recurrence at a similar time or even more rapidly than the CA125 level (EOC3 and EOC4).…”

Section: Discussionmentioning

confidence: 99%

Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer

et al. 2020

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Original ArticlePurpose The purpose of this study was to identify the clinical utility of circulating tumor DNA (ctDNA) from ascites and serial plasma samples from epithelial ovarian cancer (EOC) patients. Materials and MethodsUsing targeted next-generation sequencing, we analyzed a total of 55 EOC samples including ctDNA from ascites and serial plasma and gDNA from tumor tissues. Tumor tissues and ascites were collected during debulking surgeries and plasma samples were collected before and after the surgeries. Because one EOC patient underwent secondary debulking surgery, a total of 11 tumor tissues, 33 plasma samples, and 11 ascites samples were obtained from the 10 patients. ResultsOf the 10 patients, nine (90%) contained somatic mutations in both tumor tissues and ascites ctDNA. This mutational concordance was confirmed through correlation analysis. The mutational concordance between ascites and tumor tissues was valid in recurrent/progressive ovarian cancer. TP53 was the most frequently detected gene with mutations. ctDNA from serial plasma samples identified EOC progression/recurrence at a similar time or even more rapidly than cancer antigen 125, an established serum protein tumor marker for EOC. ConclusionOur data suggest that ascites ctDNA can be used to identify the mutational landscape of ovarian cancer for therapeutic strategy planning.

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Section: Discussionmentioning

confidence: 99%

Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer

et al. 2020

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“…Circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) isolated from blood have recently been extensively investigated as potential blood-based biomarkers for several cancer types [3][4][5]. In ovarian cancer patients, higher levels of cfDNA were found as compared to healthy donors [6,7] and patients with benign disease [1]. Higher levels of cfDNA were associated with advanced disease stage, high grade, and poorer prognosis [1,8].…”

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confidence: 99%

“…In ovarian cancer patients, higher levels of cfDNA were found as compared to healthy donors [6,7] and patients with benign disease [1]. Higher levels of cfDNA were associated with advanced disease stage, high grade, and poorer prognosis [1,8]. In addition, it has been reported in an orthotopic mouse model that progression of disease could be monitored by measuring human cfDNA.…”

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confidence: 99%

TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer

et al. 2020

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The aim of this study was to determine an optimal workflow to detect TP53 mutations in baseline and longitudinal serum cell free DNA (cfDNA) from high-grade serous ovarian carcinomas (HGSOC) patients and to define whether TP53 mutations are suitable as biomarker for disease. TP53 was investigated in tissue and archived serum from 20 HGSOC patients by a next-generation sequencing (NGS) workflow alone or combined with digital PCR (dPCR). AmpliSeq™-focused NGS panels and customized dPCR assays were used for tissue DNA and longitudinal cfDNAs, and Oncomine NGS panel with molecular barcoding was used for baseline cfDNAs. TP53 missense mutations were observed in 17 tissue specimens and in baseline cfDNA for 4/8 patients by AmpliSeq, 6/9 patients by Oncomine, and 4/6 patients by dPCR. Mutations in cfDNA were detected in 4/6 patients with residual disease and 3/4 patients with disease progression within six months, compared to 5/11 patients with no residual disease and 6/13 patients with progression after six months. Finally, mutations were detected at progression in 5/6 patients, but not during chemotherapy. NGS with molecular barcoding and dPCR were most optimal workflows to detect TP53 mutations in baseline and longitudinal serum cfDNA, respectively. TP53 mutations were undetectable in cfDNA during treatment but re-appeared at disease progression, illustrating its promise as a biomarker for disease monitoring.

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“…To our knowledge, the use of CTCs for prognosis in ovarian cancer, the deadliest of the gynecologic cancers, is in its early stages, but several studies have shown associations between CTCs and poor prognosis. 72 Because CTCs are sparse in early ovarian cancer, their presence has implications for diagnosis and treatment. However, to the best of our knowledge there are no standardized methods for their isolation and detection in the blood and only few studies to date have recruited large cohorts of patients with ovarian cancer.…”

Section: Ctcs and Gynecologic Cancersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Jin

Chen

Lan³

et al. 2019

Cancer Cytopathology

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The process of metastasis is characterized by the shedding of tumor cells into the bloodstream, where they are transported to other parts of the body to seed new tumors. These cells, known as circulating tumor cells (CTCs), have the potential to reveal much about an individual cancer case, and theoretically can aid in the prediction of outcomes and design of precision treatments. Recent advances in technology now allow for the robust and reproducible characterization of CTCs from a simple blood draw. Both the number of circulating cells and important molecular characteristics correlated with clinical phenotypes such as drug resistance can be obtained and used for real‐time prognostic analysis. Molecular characterization can provide a snapshot of the activity of the main tumor (serving as a “liquid biopsy”) and early warnings concerning changes such as the development of resistance, and aid in predicting the efficacy of different therapeutic approaches for treatment optimization. Herein, the authors review the current clinical use of CTCs as prognostic biomarkers for several different cancers. The quantification of CTCs can lead to more accurate staging and decision making regarding options such as adjuvant chemotherapy.

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Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA

Cited by 71 publications

References 88 publications

Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer

Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer

TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer

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

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