Circulating tumor cells versus circulating tumor DNA in lung cancer—which one will win?

Calabuig, Silvia; Jantus‐Lewintre, Eloísa; Herreros‐Pomares, Alejandro; Camps, Carlos

doi:10.21037/tlcr.2016.10.02

Cited by 87 publications

(98 citation statements)

References 152 publications

(193 reference statements)

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“…Although profiling of cfDNA and CTCs liquid biopsies offer convenient analysis of genetic mutations, low levels of cfDNA and CTCs in blood limit thresholds of detection. 32 Our data found mutations in 95% (19 out of 20 patients) and 75% (15 out of 20 patients) of patients by analyzing cfDNA and ctcDNA, respectively. However, simultaneous analysis of both cfDNA and ctcDNA raises this number to 100% ( Figure 3B).…”

Section: Complementary Genomic Profiling Of Cfdna and Ctcsmentioning

confidence: 50%

Analysis of miRNA inhibitors Efficacy using Capillary Electrophoresis with Laser-Induced Fluorescence

Chae

Ban

2019

Preprint

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Background: Cell-free circulating DNA (cfDNA) and circulating tumor cells (CTCs) are emerging minimally invasive cancer biomarkers that help with early diagnosis, prognosis and therapeutic target selection. Combined use of cfDNA and CTCs provides complementary information about tumor cell heterogeneity thus helping to identify genetic mutations relevant in clinical decision making.Patients and methods: cfDNA and CTCs were isolated from whole blood specimens of 20 gynecological cancer patients by CD-PRIME™. We performed targeted sequencing across 51 actionable genes in 20 cfDNA and ctcDNA, and then analyzed genetic mutations and clinical significance.Results: A total of 33 somatic variants were found in 16 actionable genes. A genetic variant analysis revealed 15 somatic variants in the cfDNA and 20 somatic variants in CTCs sample, only two variants were found in common. The most frequently altered genes in cfDNA samples were TP53, PTCH1, FGFR, and BRCA2. in contrast, the most frequently altered genes in CTCs sample were TP53, BRCA1, TSC2, ERBB2 and PTCH1. An in silico analysis revealed that 60% of somatic variants (20 out of 33) were potentially pathogenic mutations as expected. Detected BRCA1 p.S573 frameshift mutation and BRCA2 p.Q1683 nonsense mutation lead to loss-of-function of BRCA1 and BRCA2. Conclusion:Our study shows that the genetic profiling of cfDNA and CTCs together provides more enriched genomic information for guiding preclinical and clinical strategies and targeted therapies.Studies have reported advantages such as concordance between genetic mutation in CTCs and primary tissue 13 , and extensive information about DNA, RNA and protein. 14,15 Hence, the isolation and detection of CTCs offers one of the most promising methods for accurate and precise diagnosing many cancers and predicting metastasis. [16][17][18] As cfDNA and CTCs possess different analytical properties, when analyzed in combination, may provide complementary and augmented information on tumor cell heterogeneity that is critical in identifying key molecular targets for improved cancer therapies. 19 Gynecologic cancer is a cancer developed in female reproductive organs. Each gynecologic cancer has different signs, symptoms, and causes. Early detection of gynecologic cancer and an understanding of specific mutations involved can lead to more effective treatments. In this study, we performed targeted sequencing of a customized cancer panel of 51 actionable genes in cfDNA and CTCs samples of gynecologic cancers, including vulvar, endometrial, ovarian, cervical and uterine cancers. This study shows that the actionable mutations of cfDNA and CTCs from patients can be readily profiled using NGS, making them available for clinical application in guiding treatment decisions during diagnosis, disease monitoring and recommending the appropriate drug for each individual patient over time through non-invasive assays.

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Section: Complementary Genomic Profiling Of Cfdna and Ctcsmentioning

confidence: 50%

Analysis of miRNA inhibitors Efficacy using Capillary Electrophoresis with Laser-Induced Fluorescence

Chae

Ban

2019

Preprint

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“…Fluorescence in situ hybridization (FISH) analysis can be used to detect gene translocation. 47 Multiregion genetic analysis of renal carcinomas revealed intratumour heterogeneity. 48 The phylogenetic reconstruction of those renal carcinomas also revealed branched evolutionary tumour growth, with 63%-69% of unique somatic mutations present in various tumour regions.…”

Section: Intratumour Genetic Heterogeneity and Parallel Tumour Evolmentioning

confidence: 99%

Disseminated tumour cells in bone marrow are the source of cancer relapse after therapy

Sai

Xiang

2018

J Cellular Molecular Medi

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Accumulating evidence indicates that cancer cells spread much earlier than was previously believed. Recent technological advances have greatly improved the detection methods of circulating tumour cells (CTCs), suggesting that the dissemination of cancer cells into the circulation occurs randomly. Most CTCs die in circulation as a result of shear stress and/or anoikis. However, the persistence of disseminated tumour cells (DTCs) in the bone marrow is the result of interaction of DTCs with bone marrow microenvironment. DTCs in the bone marrow undergo successive clonal expansions and a parallel progression that leads to new variants. Compared to the CTCs, DTCs in the bone marrow have a unique signature, which displayed dormant, mesenchymal phenotype and osteoblast‐like or osteoclast‐like phenotype. The persistence of DTCs in the bone marrow is always related to minimal residual diseases (MRDs). This review outlines the difference between CTCs and DTCs in the bone marrow and describes how this difference affects the clinical values of CTCs and DTCs, such as metastasis and recurrence. We suggest that DTCs remaining in the bone marrow after therapy can be used as a superior marker in comparison with CTCs to define patients with an unfavourable prognosis and may therefore be a potential prognostic factor and therapeutic target for cancer therapy.

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“…For example, in lung cancer liquid biopsies, blood samples are mainly used as a sample source for analyzing CTCs or ctDNA, in addition to other biomarkers of interest, such as circulating microRNAs, circulating RNA, platelets, plasma/serum metabolites, or exosomes. [15] The use of CTC as a prognostic biomarker is already well established in cancers of the breast, colon, and prostate. The potential clinical benefits of a liquid biopsy may be seen in early detection of cancers, real-time response to therapy, detection of developing resistance, prognosis, and tumor heterogeneity analysis.…”

Section: Liquid Biopsymentioning

confidence: 99%

Precision medicine in oncology – On a journey from dreams to reality

Patel

Shah

2018

Int J Mol Immuno Oncol.

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Precision medicine is defined as treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from another patient with similar clinical presentation. Precision Oncology is an innovation at the cusp of blooming. We reviewed the status of precision oncology today, and discuss the flaws, mainly in next-generation sequencing (NGS) and the design of clinical trials thus far. Precision oncology although paints a glossy imagery, the reality is laden with inherent flaws, lack of guided research and a generalisability for the clinical market. The scenario in India is similar. It remains to be seen, if Precision Oncology is able to withstand the scrutiny likely to come its way, and if it can appeal largely to a complex socioeconomic market as India. We conclude that precision oncology is not far from an exponential boom, provided the right questions are asked, and answers derived.

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Circulating tumor cells versus circulating tumor DNA in lung cancer—which one will win?

Cited by 87 publications

References 152 publications

Analysis of miRNA inhibitors Efficacy using Capillary Electrophoresis with Laser-Induced Fluorescence

Analysis of miRNA inhibitors Efficacy using Capillary Electrophoresis with Laser-Induced Fluorescence

Disseminated tumour cells in bone marrow are the source of cancer relapse after therapy

Precision medicine in oncology – On a journey from dreams to reality

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