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16 pages, 5791 KiB

Open AccessArticle

by Hsueh-Yao Chu, Chih-Yung Yang, Ping-Hao Yeh, Chun-Jieh Hsu, Lu-Wei Chang, Wei-Jen Chan, Chien-Ping Lin, You-You Lyu, Wei-Cheng Wu, Chun-Wei Lee, Jen-Kuei Wu, Jeng-Kai Jiang and Fan-Gang Tseng

Cells 2021, 10(5), 1149; https://doi.org/10.3390/cells10051149 - 10 May 2021

Cited by 20 | Viewed by 3270

Abstract

Circulation tumor cells (CTCs) play an important role in metastasis and highly correlate with cancer progression; thus, CTCs could be considered as a powerful diagnosis tool. Our previous studies showed that the number of CTCs could be utilized for recurrence prediction in colorectal [...] Read more.

Circulation tumor cells (CTCs) play an important role in metastasis and highly correlate with cancer progression; thus, CTCs could be considered as a powerful diagnosis tool. Our previous studies showed that the number of CTCs could be utilized for recurrence prediction in colorectal cancer (CRC); however, the odds ratio was still lower than five. To improve prognosis in CRC patients, we analyzed CTC clusters/microemboli, CTC numbers, and carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9) levels using a self-assembled cell array (SACA) chip system for recurrence prediction. In CRC patients, the presence of CTC clusters/microemboli may have higher correlation in metastasis when compared to the high number of CTCs. Additionally, when both the number of CTCs and serum CEA levels are high, very high odds ratios of 24.4 and 17.1 are observed in patients at all stages and stage III of CRC, respectively. The high number of CTCs and CTC clusters/microemboli simultaneously suggests the high chance of relapse (odds ratio 8.4). Overall, the characteristic of CTC clusters/microemboli, CEA level, and CTC number have a clinical potential to enhance CRC prognosis. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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22 pages, 5517 KiB

Open AccessFeature PaperArticle

Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients

by Corinna Keup, Vinay Suryaprakash, Markus Storbeck, Oliver Hoffmann, Rainer Kimmig and Sabine Kasimir-Bauer

Cells 2021, 10(2), 212; https://doi.org/10.3390/cells10020212 - 21 Jan 2021

Cited by 27 | Viewed by 3800

Abstract

Dynamics of mRNA from circulating tumor cells (CTCs), mRNA from extracellular vesicles (EVs), and cell-free DNA (cfDNA) were assessed to examine the relevance of a longitudinal multi-parametric liquid biopsy strategy. Eighteen milliliters of blood was drawn from 27 hormone receptor-positive and human epidermal [...] Read more.

Dynamics of mRNA from circulating tumor cells (CTCs), mRNA from extracellular vesicles (EVs), and cell-free DNA (cfDNA) were assessed to examine the relevance of a longitudinal multi-parametric liquid biopsy strategy. Eighteen milliliters of blood was drawn from 27 hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients at disease progression and at two subsequent radiologic staging time points. CTC mRNA and EV mRNA were analyzed using multi-marker qPCR, and cfDNA was analyzed using targeted next-generation sequencing (NGS). The presence of ERBB2 or ERBB3 overexpression signals in CTCs significantly correlated with disease progression (87% specificity, 36% sensitivity, p-value = 0.023), and the presence of either ERBB3 signals in CTCs or EVs or cfDNA variants in ERBB3 also showed a significant association with progressive MBC. Fluctuations during treatment were detected in the EV fraction with the appearance of hitherto undetected ERCC1 signals correlating with progressive disease (97% specificity, 18% sensitivity, p-value = 0.030). Allele frequency development of ESR1 and PIK3CA variants detected at subsequent staging time points could be used as a predictor for therapy success and, importantly, might help guide therapy decisions. The three analytes, each with their own unique features for disease monitoring, were shown to be complementary, underlining the usefulness of the longitudinal multi-parametric liquid biopsy approach. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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17 pages, 1879 KiB

Open AccessArticle

Endothelium-Derived Extracellular Vesicles Associate with Poor Prognosis in Metastatic Colorectal Cancer

by Afroditi Nanou, Linda Mol, Frank A. W. Coumans, Miriam Koopman, Cornelis J. A. Punt and Leon W. M. M. Terstappen

Cells 2020, 9(12), 2688; https://doi.org/10.3390/cells9122688 - 15 Dec 2020

Cited by 12 | Viewed by 2743

Abstract

Elevated, tumor-derived extracellular vesicle (tdEV) and circulating tumor cell (CTC) loads in metastatic cancer are associated with poor clinical outcome. Herein, we investigate whether endothelium-derived extracellular vesicles (edEVs) can be detected in the blood of metastatic colorectal cancer (mCRC) patients, and whether those [...] Read more.

Elevated, tumor-derived extracellular vesicle (tdEV) and circulating tumor cell (CTC) loads in metastatic cancer are associated with poor clinical outcome. Herein, we investigate whether endothelium-derived extracellular vesicles (edEVs) can be detected in the blood of metastatic colorectal cancer (mCRC) patients, and whether those vesicles associate with prognosis. The open-source ACCEPT (Automated CTC Classification, Enumeration, and Phenotyping) software was used to enumerate edEVs, tdEVs, and other objects from digitally stored CellSearch images acquired after CTC and circulating endothelial cell (CEC) enrichment from the blood of 395 mCRC patients before the initiation of a new therapy. Patients had participated in the prospective phase III CAIRO2 study. The presence of edEVs was found 5- to 10-fold higher than CECs. The hazard ratio (HR) (95% CI) of progression-free survival (PFS) for increased CTCs (≥3 in 7.5 mL), tdEVs (≥40 in 7.5 mL), and edEVs (≥287 in 4.0 mL.) was 1.4 (1.1–1.9), 2.0 (1.5–2.6), and 1.7 (1.2–2.5), respectively. The HR of Overall Survival (OS) for increased CTCs, tdEVs and edEVs was 2.2 (1.7–3.0), 2.7 (2.0–3.5), and 2.1 (1.5–2.8), respectively. There was no cut-off value for CECs, leading to a dichotomization of patients with a significant HR. Only tdEVs remained a significant predictor of OS in the final multivariable model. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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18 pages, 1232 KiB

Open AccessArticle

Detection of KRAS G12/G13 Mutations in Cell Free-DNA by Droplet Digital PCR, Offers Prognostic Information for Patients with Advanced Non-Small Cell Lung Cancer

by Kleita Michaelidou, Chara Koutoulaki, Konstantinos Mavridis, Eleftherios Vorrias, Maria A. Papadaki, Anastasios V. Koutsopoulos, Dimitrios Mavroudis and Sofia Agelaki

Cells 2020, 9(11), 2514; https://doi.org/10.3390/cells9112514 - 20 Nov 2020

Cited by 17 | Viewed by 3759

Abstract

KRAS mutations are found in approximately one third of non-small cell lung cancer (NSCLC) patients. In this study, we aim to investigate whether KRAS G12/G13 mutant allele fraction (MAF) in cell-free DNA (cfDNA) can provide meaningful prognostic information in NSCLC. Multiplex droplet-digital PCR [...] Read more.

KRAS mutations are found in approximately one third of non-small cell lung cancer (NSCLC) patients. In this study, we aim to investigate whether KRAS G12/G13 mutant allele fraction (MAF) in cell-free DNA (cfDNA) can provide meaningful prognostic information in NSCLC. Multiplex droplet-digital PCR was used to quantitatively assess KRAS G12/G13 MAF in cfDNA from 114 pre-treated advanced disease NSCLC patients. In 14 patients, changes in KRAS G12/G13 MAF were longitudinally monitored during treatment. Plasma KRAS G12/G13 status was associated with poor patients’ outcome in terms of progression-free survival (PFS) (p < 0.001) and overall survival (OS) (p < 0.001). In multivariate analysis, the detection of plasma KRAS mutations was an independent predictor of adverse PFS (HR = 3.12; p < 0.001) and OS (HR = 2.53; p = 0.002). KRAS G12/G13 MAF at first treatment evaluation (T1) was higher (p = 0.013) among patients experiencing progressive disease compared to those with disease control, and increased KRAS MAF at T1 was associated (p = 0.005) with shorter PFS. On the contrary, no association was observed between tissue KRAS mutation status and patients’ prognosis. Our results show that ddPCR-based detection of KRAS G12/G13 mutations in plasma could serve as an independent biomarker of unfavorable prognosis in NSCLC patients. Changes in KRAS MAF can provide valuable information for monitoring patient outcome during treatment. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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13 pages, 3294 KiB

Open AccessArticle

Discovery of Targetable Genetic Alterations in NSCLC Patients with Different Metastatic Patterns Using a MassARRAY-Based Circulating Tumor DNA Assay

by Yassine Belloum, Melanie Janning, Malte Mohme, Ronald Simon, Jolanthe Kropidlowski, Alexander Sartori, Darryl Irwin, Manfred Westphal, Katrin Lamszus, Sonja Loges, Sabine Riethdorf, Klaus Pantel and Harriet Wikman

Cells 2020, 9(11), 2337; https://doi.org/10.3390/cells9112337 - 22 Oct 2020

Cited by 15 | Viewed by 4372

Abstract

Circulating tumor DNA (ctDNA) has shown great promise as a minimally invasive liquid biopsy for personalized cancer diagnostics especially among metastatic patients. Here, we used a novel sensitive assay to detect clinically relevant mutations in ctDNA in blood plasma from metastatic non-small cell [...] Read more.

Circulating tumor DNA (ctDNA) has shown great promise as a minimally invasive liquid biopsy for personalized cancer diagnostics especially among metastatic patients. Here, we used a novel sensitive assay to detect clinically relevant mutations in ctDNA in blood plasma from metastatic non-small cell lung cancer (NSCLC) patients, including patients with a limited oligo–brain metastatic disease. We analyzed 66 plasma samples from 56 metastatic NSCLC patients for 74 hotspot mutations in five genes commonly mutated in NSCLC using a novel MassARRAY-based lung cancer panel with a turnaround time of only 3 days. Mutations in plasma DNA could be detected in 28 out of 56 patients (50.0%), with a variant allele frequency (VAF) ranging between 0.1% and 5.0%. Mutations were detected in 50.0% of patients with oligo–brain metastatic disease, although the median VAF was lower (0.4%) compared to multi-brain metastatic patients (0.9%) and patients with extra-cranial metastatic progression (1.2%). We observed an overall concordance of 86.4% (n = 38/44) for EGFR status between plasma and tissue. The MassARRAY technology can detect clinically relevant mutations in plasma DNA from metastatic NSCLC patients including patients with limited, oligo–brain metastatic disease. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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15 pages, 4601 KiB

Open AccessArticle

MiRNA let-7 from TPO(+) Extracellular Vesicles is a Potential Marker for a Differential Diagnosis of Follicular Thyroid Nodules

by Lidia Zabegina, Inga Nazarova, Margarita Knyazeva, Nadezhda Nikiforova, Maria Slyusarenko, Sergey Titov, Dmitry Vasilyev, Ilya Sleptsov and Anastasia Malek

Cells 2020, 9(8), 1917; https://doi.org/10.3390/cells9081917 - 18 Aug 2020

Cited by 18 | Viewed by 4517

Abstract

Background: The current approaches to distinguish follicular adenomas (FA) and follicular thyroid cancer (FTC) at the pre-operative stage have low predictive value. Liquid biopsy-based analysis of circulating extracellular vesicles (EVs) presents a promising diagnostic method. However, the extreme heterogeneity of plasma EV population [...] Read more.

Background: The current approaches to distinguish follicular adenomas (FA) and follicular thyroid cancer (FTC) at the pre-operative stage have low predictive value. Liquid biopsy-based analysis of circulating extracellular vesicles (EVs) presents a promising diagnostic method. However, the extreme heterogeneity of plasma EV population hampers the development of new diagnostic tests. We hypothesize that the isolation of EVs with thyroid-specific surface molecules followed by miRNA analysis, may have improved diagnostic potency. Methods: The total population of EVs was isolated from the plasma of patients with FA (n = 30) and FTC (n = 30). Thyroid peroxidase (TPO)-positive EVs were isolated from the total populations using immune-beads. The miRNA from the TPO(+)EVs obtained from the plasma of FA and FTC patients was assayed by RT-PCR. The diagnostic potency of the selected miRNAs was estimated by the receiver operating characteristic (ROC) analysis. Results: TPO(+)EVs can be efficiently isolated by immunobeads. The analysis of Let-7 family members in TPO(+)EVs allows one to distinguish FA and FTC with high accuracy (area under curve defined by ROC = 0.77–0.84). Conclusion: The isolation of TPO(+)EVs, followed by RT-qPCR analysis of Let-7 family members, may present a helpful approach to manage follicular nodules in the thyroid gland. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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17 pages, 2147 KiB

Open AccessArticle

The Distribution of Circulating Tumor Cells Is Different in Metastatic Lobular Compared to Ductal Carcinoma of the Breast—Long-Term Prognostic Significance

by Ulrik Narbe, Pär-Ola Bendahl, Kristina Aaltonen, Mårten Fernö, Carina Forsare, Charlotte Levin Tykjær Jørgensen, Anna-Maria Larsson and Lisa Rydén

Cells 2020, 9(7), 1718; https://doi.org/10.3390/cells9071718 - 17 Jul 2020

Cited by 12 | Viewed by 3390

Abstract

Background: Invasive lobular carcinoma (ILC) has distinguishing features when compared to invasive ductal carcinoma of no special type (NST). In this study, we explored the distributional and prognostic characteristics of circulating tumor cells (CTCs) in metastatic ILC and NST. Materials and methods: Patients [...] Read more.

Background: Invasive lobular carcinoma (ILC) has distinguishing features when compared to invasive ductal carcinoma of no special type (NST). In this study, we explored the distributional and prognostic characteristics of circulating tumor cells (CTCs) in metastatic ILC and NST. Materials and methods: Patients were included in an observational trial (ClinicalTrials.gov NCT01322893) with ILC (n = 28) and NST (n = 111). CTC count (number/7.5 mL blood) was evaluated with serial sampling (CellSearch). The primary endpoint was progression-free survival (PFS). Results: The CTC counts were higher in ILC (median 70) than in NST cases (median 2) at baseline (p < 0.001). The evidence for ≥5 CTCs as a prognostic factor for PFS in ILC was weak, but stronger with higher cut-offs (CTC ≥ 20: hazard ratio (HR) 3.0, p = 0.01) (CTC ≥ 80: HR 3.6, p = 0.004). In NST, however, the prognostic effect of CTCs ≥5 was strong. Decline in CTC count from baseline to three months was associated with improved prognosis in ILC and NST. Conclusions: The number of CTCs is higher in ILC than in NST, implying that a higher CTC cut-off could be considered for ILC when applying the CellSearch technique. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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19 pages, 2307 KiB

Open AccessArticle

Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer

by Manuel Abreu, Pablo Cabezas-Sainz, Lorena Alonso-Alconada, Alba Ferreirós, Patricia Mondelo-Macía, Ramón Manuel Lago-Lestón, Alicia Abalo, Eva Díaz, Sara Palacios-Zambrano, Alejandro Rojo-Sebastian, Rafael López-López, Laura Sánchez, Gema Moreno-Bueno and Laura Muinelo-Romay

Cells 2020, 9(5), 1218; https://doi.org/10.3390/cells9051218 - 14 May 2020

Cited by 22 | Viewed by 3907

Abstract

Background: Recent studies showed a relevant role of hematogenous spread in ovarian cancer and the interest of circulating tumor cells (CTCs) monitoring as a prognosis marker. The aim of the present study was the characterization of CTCs from ovarian cancer patients, paying special [...] Read more.

Background: Recent studies showed a relevant role of hematogenous spread in ovarian cancer and the interest of circulating tumor cells (CTCs) monitoring as a prognosis marker. The aim of the present study was the characterization of CTCs from ovarian cancer patients, paying special attention to cell plasticity characteristics to better understand the biology of these cells. Methods: CTCs isolation was carried out in 38 patients with advanced high-grade serous ovarian cancer using in parallel CellSearch and an alternative EpCAM-based immunoisolation followed by RT-qPCR analysis to characterize these cells. Results: Epithelial CTCs were found in 21% of patients, being their presence higher in patients with extraperitoneal metastasis. Importantly, this population was characterized by the expression of epithelial markers as MUC1 and CK19, but also by genes associated with mesenchymal and more malignant features as TIMP1, CXCR4 and the stem markers CD24 and CD44. In addition, we evidenced the relevance of TIMP1 expression to promote tumor proliferation, suggesting its interest as a therapeutic target. Conclusions: Overall, we evidenced the utility of the molecular characterization of EpCAM⁺ CTCs from advanced ovarian cancer patients to identify biomarkers with potential applicability for disseminated disease detection and as therapeutic targets such as TIMP1. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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18 pages, 4642 KiB

Open AccessArticle

Detection of MET Alterations Using Cell Free DNA and Circulating Tumor Cells from Cancer Patients

by Patricia Mondelo-Macía, Carmela Rodríguez-López, Laura Valiña, Santiago Aguín, Luis León-Mateos, Jorge García-González, Alicia Abalo, Oscar Rapado-González, Mercedes Suárez-Cunqueiro, Angel Díaz-Lagares, Teresa Curiel, Silvia Calabuig-Fariñas, Aitor Azkárate, Antònia Obrador-Hevia, Ihab Abdulkader, Laura Muinelo-Romay, Roberto Diaz-Peña and Rafael López-López

Cells 2020, 9(2), 522; https://doi.org/10.3390/cells9020522 - 24 Feb 2020

Cited by 23 | Viewed by 4754

Abstract

MET alterations may provide a potential biomarker to evaluate patients who will benefit from treatment with MET inhibitors. Therefore, the purpose of the present study is to investigate the utility of a liquid biopsy-based strategy to assess MET alterations in cancer patients. We [...] Read more.

MET alterations may provide a potential biomarker to evaluate patients who will benefit from treatment with MET inhibitors. Therefore, the purpose of the present study is to investigate the utility of a liquid biopsy-based strategy to assess MET alterations in cancer patients. We analyzed MET amplification in circulating free DNA (cfDNA) from 174 patients with cancer and 49 healthy controls and demonstrated the accuracy of the analysis to detect its alteration in patients. Importantly, a significant correlation between cfDNA concentration and MET copy number (CN) in cancer patients (r = 0.57, p <10⁻¹⁰) was determined. Furthermore, we evaluated two approaches to detect the presence of MET on circulating tumor cells (CTCs), using the CellSearch^® and Parsortix systems and monitored patients under anti-EGFR treatment (n = 30) combining both cfDNA and CTCs analyses. This follow-up provides evidence for the potential of MET CN assessment when patients develop resistance to anti-EGFR therapy and a significant association between the presence of CTCs MET⁺ and the Overall Survival (OS) in head and neck cancer patients (P = 0.05; HR = 6.66). In conclusion, we develop specific and noninvasive assays to monitor MET status in cfDNA/CTCs and demonstrate the utility of plasma MET CN determination as a biomarker for monitoring the appearance of resistance to anti-EGFR therapy. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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Review

Jump to: Research

14 pages, 515 KiB

Open AccessReview

Next-Generation Sequencing on Circulating Tumor DNA in Advanced Solid Cancer: Swiss Army Knife for the Molecular Tumor Board? A Review of the Literature Focused on FDA Approved Test

by Damien Vasseur, Hela Sassi, Arnaud Bayle, Marco Tagliamento, Benjamin Besse, Christophe Marzac, Ahmadreza Arbab, Nathalie Auger, Sophie Cotteret, Mihaela Aldea, Félix Blanc-Durand, Arthur Géraud, Anas Gazzah, Yohann Loriot, Antoine Hollebecque, Patricia Martín-Romano, Maud Ngo-Camus, Claudio Nicotra, Santiago Ponce, Madona Sakkal, Olivier Caron, Cristina Smolenschi, Jean-Baptiste Micol, Antoine Italiano, Etienne Rouleau and Ludovic Lacroix Show full author list Hide full author list

Cells 2022, 11(12), 1901; https://doi.org/10.3390/cells11121901 - 11 Jun 2022

Cited by 14 | Viewed by 4965

Abstract

FDA-approved next-generation sequencing assays based on cell-free DNA offers new opportunities in a molecular-tumor-board context thanks to the noninvasiveness of liquid biopsy, the diversity of analyzed parameters and the short turnaround time. It gives the opportunity to study the heterogeneity of the tumor, [...] Read more.

FDA-approved next-generation sequencing assays based on cell-free DNA offers new opportunities in a molecular-tumor-board context thanks to the noninvasiveness of liquid biopsy, the diversity of analyzed parameters and the short turnaround time. It gives the opportunity to study the heterogeneity of the tumor, to elucidate complex resistance mechanisms and to adapt treatment strategies. However, lowering the limit of detection and increasing the panels’ size raise new questions in terms of detection of incidental germline alterations, occult malignancies and clonal hematopoiesis of indeterminate potential mutations. In this review, after a technological discussion and description of the common problematics encountered, we establish recommendations in properly using these FDA-approved tests in a molecular-tumor-board context. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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15 pages, 1380 KiB

Open AccessReview

Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic Instability

by Tala Tayoun, Marianne Oulhen, Agathe Aberlenc, Françoise Farace and Patrycja Pawlikowska

Cells 2021, 10(2), 337; https://doi.org/10.3390/cells10020337 - 5 Feb 2021

Cited by 7 | Viewed by 2808

Abstract

Circulating tumor cells (CTCs) provide an accessible tool for investigating tumor heterogeneity and cell populations with metastatic potential. Although an in-depth molecular investigation is limited by the extremely low CTC count in circulation, significant progress has been made recently in single-cell analytical processes. [...] Read more.

Circulating tumor cells (CTCs) provide an accessible tool for investigating tumor heterogeneity and cell populations with metastatic potential. Although an in-depth molecular investigation is limited by the extremely low CTC count in circulation, significant progress has been made recently in single-cell analytical processes. Indeed, CTC monitoring through molecular and functional characterization may provide an understanding of genomic instability (GI) molecular mechanisms, which contribute to tumor evolution and emergence of resistant clones. In this review, we discuss the sources and consequences of GI seen through single-cell analysis of CTCs in different types of tumors. We present a detailed overview of chromosomal instability (CIN) in CTCs assessed by fluorescence in situ hybridization (FISH), and we reveal utility of CTC single-cell sequencing in identifying copy number alterations (CNA) oncogenic drivers. We highlight the role of CIN in CTC-driven metastatic progression and acquired resistance, and we comment on the technical obstacles and challenges encountered during single CTC analysis. We focus on the DNA damage response and depict DNA-repair-related dynamic biomarkers reported to date in CTCs and their role in predicting response to genotoxic treatment. In summary, the suggested relationship between genomic aberrations in CTCs and prognosis strongly supports the potential utility of GI monitoring in CTCs in clinical risk assessment and therapeutic choice. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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16 pages, 1833 KiB

Open AccessReview

Detecting Resistance to Therapeutic ALK Inhibitors in Tumor Tissue and Liquid Biopsy Markers: An Update to a Clinical Routine Practice

by Paul Hofman

Cells 2021, 10(1), 168; https://doi.org/10.3390/cells10010168 - 15 Jan 2021

Cited by 27 | Viewed by 4105

Abstract

The survival of most patients with advanced stage non-small cell lung cancer is prolonged by several months when they are treated with first- and next-generation inhibitors targeting ALK rearrangements, but resistance inevitably emerges. Some of the mechanisms of resistance are sensitive to novel [...] Read more.

The survival of most patients with advanced stage non-small cell lung cancer is prolonged by several months when they are treated with first- and next-generation inhibitors targeting ALK rearrangements, but resistance inevitably emerges. Some of the mechanisms of resistance are sensitive to novel ALK inhibitors but after an initial tumor response, more or less long-term resistance sets in. Therefore, to adapt treatment it is necessary to repeat biological sampling over time to look for different mechanisms of resistance. To this aim it is essential to obtain liquid and/or tissue biopsies to detect therapeutic targets, in particular for the analysis of different genomic alterations. This review discusses the mechanisms of resistance to therapeutics targeting genomic alterations in ALK as well as the advantages and the limitations of liquid biopsies for their identification. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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20 pages, 1758 KiB

Open AccessReview

Liquid Biopsy in Small Cell Lung Cancer—A Route to Improved Clinical Care?

by Matt Church, Louise Carter and Fiona Blackhall

Cells 2020, 9(12), 2586; https://doi.org/10.3390/cells9122586 - 3 Dec 2020

Cited by 5 | Viewed by 2871

Abstract

Small cell lung cancer (SCLC) has a particularly poor prognosis despite the high initial response to first-line systemic therapy, and there is a well-recognised lack of meaningful treatments beyond the second line. A number of reasons have been put forward to explain this, [...] Read more.

Small cell lung cancer (SCLC) has a particularly poor prognosis despite the high initial response to first-line systemic therapy, and there is a well-recognised lack of meaningful treatments beyond the second line. A number of reasons have been put forward to explain this, including a lack of common, easily-druggable genetic mutations in SCLC and rarity of high-quality tissue samples due to late presentation. Liquid biopsies, including circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) are increasingly used as surrogates for tumour tissue and have the advantage of being easily obtained serially to inform on the biology of disease progression and acquired chemoresistance, and may provide a pathway to improve care in this notoriously refractory disease. Here we discuss the current evidence behind these liquid biopsy methods in SCLC, and how they could be employed in future clinical care. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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12 pages, 1014 KiB

Open AccessReview

Liquid Biopsy of Non-Plasma Body Fluids in Non-Small Cell Lung Cancer: Look Closer to the Tumor!

by Lucile Durin, Anne Pradines, Céline Basset, Bryan Ulrich, Laura Keller, Vincent Dongay, Gilles Favre, Julien Mazieres and Nicolas Guibert

Cells 2020, 9(11), 2486; https://doi.org/10.3390/cells9112486 - 16 Nov 2020

Cited by 19 | Viewed by 4661

Abstract

Liquid biopsy is a rapidly emerging field due to an increasing number of oncogenic drivers and a better understanding of resistance mechanisms to targeted therapies in non-small cell lung cancer (NSCLC). The sensitivity of the most widely used blood-based assays is, however, limited [...] Read more.

Liquid biopsy is a rapidly emerging field due to an increasing number of oncogenic drivers and a better understanding of resistance mechanisms to targeted therapies in non-small cell lung cancer (NSCLC). The sensitivity of the most widely used blood-based assays is, however, limited in particular in cases of low tumor volume where shed of tumor-derived material can be limited. A negative result thus requires biopsy confirmation using minimally invasive sampling procedures that can result in small specimens, which are often not suitable for genotyping. Liquid biopsy is not limited to plasma, and tumor DNA circulating in other body fluids such as urine, pleural fluid, cerebrospinal fluid, or cytology specimen-derived supernatant can be exploited. In comparison to cell blocks, these fluids in close contact to the tumor may contain a more abundant and less analytically demanding tumor DNA. In this review, we discuss the potential applications of circulating tumor DNA derived from cytology samples in NSCLC, from early stage (screening, nodule characterization) to metastatic disease. Full article

(This article belongs to the Special Issue Liquid Biopsy)

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