Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation
Abstract
:Simple Summary
Abstract
1. Introduction
2. Non-Small Cell (NSCLC) and Small Cell (SCLC) Lung Cancer
3. Circulating Cancer Biomarkers
3.1. Circulating Tumor Cells (CTCs)
3.2. Circulating Tumor DNA (ctDNA)
4. Lab-on-a-Chip Approaches for Liquid Biopsies
4.1. Microfluidic-Assisted Strategies in CTCs Research
4.2. Microfluidic-Assisted Strategies in ctDNA Research
5. Clinical Validation and Trials in Lung Cancer
6. Concluding Remarks and Future Perspectives
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Name/NTC | Status | Condition/Patients (n) | Brief Summary |
---|---|---|---|
Development of Circulating Tumor Cell Molecular Diagnostics Using a Novel Microfluidic Device NCT01193829 | Completed (2014) | NSCLC n = 30 | To compare EGFR mutations between NSCLC and corresponding CTCs isolated by a label-free microfluidic device-based system. The device was tested for the feasibility to detect clinically relevant EGFR mutations in CTCs. |
Detecting EGFR T790M Mutations from Circulating Tumor Cells NCT01734915 | Completed (2016) | NSCLC with EGFR mutation n = 40 | To determine whether the EGFR mutation can be detected in CTCs and if it reliably compares to tissue biopsy results. The CTC-chip was applied to isolate CTCs and identify the EGFR mutation in a less invasive way, aiming at facilitating the diagnosis of lung cancer. |
A Study to Isolate and Test Circulating Tumor Cells Using the ClearCell® FX EP+ System NCT02370303 | Completed (2018) | Stage IV LCa Stage IB or higher NSCLC n = 23 | To isolate and quantify CTCs of lung cancer patients using the ClearCell® FX EP+ System, to advance cancer detection and treatment monitoring. For this, both blood and tumor samples were evaluated. Additionally, postoperative CTCs levels were assessed. |
PDL-1 Expression on Circulating Tumor Cells in Non-small Cell Lung Cancer (IMMUNO-PREDICT) NCT02827344 | Recruiting | Stage IV NSCLC n= 200 | To demonstrate the feasibility of the analysis of PD-L1 expression on CTCs isolated by ISET filtration module. |
Circulating Tumor Cells in Lung Cancer Screening (AIR) NCT02500693 | Unknown | High-risk patients n = 600 | To evaluate the predictive value of CTC detection for the diagnosis of lung cancer with the ISET technology. |
Circulating Tumor Cells Spillage After Pulmonary Biopsy NCT02507778 | Unknown | LCa n = 40 | To quantify the number of CTCs and correlate with the tumor response to chemotherapy. Here, the CellCollectorTM, which detects and isolates EpCAM+ CTCs is applied. |
Application of Detecting Circulating Tumor Cells in the Accurate Treatment of Early Stage Lung Adenocarcinoma (CTCs detection) NCT02951897 | Unknown | Stage I Adenocarcinoma n = 120 | To explore whether CTCs detection in patients diagnosed with early-stage lung cancer, and prior to surgery, can aid with early diagnosis or contribute to predict the prognosis and treatment strategies. The CanPatrolTM technology is applied for CTCs enrichment. |
The Method ISET (Insulation by Size of Epithelial Tumor Cells) NCT00818558 | Unknown | NSCLC n = 520 | To evaluate the potential of ISET method to preoperative detection of CTC in patients with NSCLC. Furthermore, to correlate the presence of CTCs with pTNM stage, histology, and primary tumor cellularity. |
Name/NTC | Status | Condition/Patients (n) | Brief Summary |
---|---|---|---|
Europe-Japan Diagnostic Study for EGFR Testing (ASSESS) NCT01785888 | Completed (2016) | Stage IIIA/B or metastatic NSCLC n = 1311 | To assess the concordance of EGFR mutation status derived from tumor samples and blood-based cfDNA. |
T790M Mutation on ctDNA in Patients with NSCLC After EGFR-TKI Failure NCT02418234 | Completed (2018) | Metastatic/stage III NSCLC n = 314 | To compare the frequency and abundance of T90M mutation using ARMS and ddPCR among different clinical modes of NSCLC patients with EGFR-TKI failure. |
Study to Evaluate Concordance of Detecting EGFR Mutation by Circulating Tumor Free DNA Versus Tissues Biopsy in NSCLC. NCT03562819 | Completed (2019) | Adenocarcinoma n = 269 | To assess EGFR mutation status by circulation tumor free DNA in advanced NSCLC patients comparing to adenocarcinoma histology. |
LIquid BIopsies in Patients Presenting Non-small Cell Lung Cancer (LIBIL) NCT02511288 | Recruiting | Stage IIIB/IV NSCLC n = 900 | To characterize the genetic profile of patients with advanced stage NSCLC through ctDNA using ddPCR and targeted NGF, whole genome sequencing. |
Evaluation of the Feasibility and Clinical Relevance of Liquid Biopsy in Patients with Suspicious Metastatic Lung Cancer (LIBELULE) NCT03721120 | Recruiting | Metastatic LCa n= 286 | To perform genomic analyses of cfDNA using the InVision® technology, by profiling the presence of genomic aberrations in a panel of 35 genes, including all actionable alterations required to initiate the appropriate first-line therapy (EGFR, ALK, ROS1, and BRAF V600E). |
TR(ACE) Assay Clinical Specimen Study NCT02934360 | Unknown | NSCLC n = 450 | To evaluate the TR(ACE) Assay as a method of diagnostic, monitoring disease progress and response to therapy. This assay is a quantitative in vitro diagnostic test run in the TR(ACE) instrument that uses an electrokinetic technique to selectively capture cfDNA and others cellular debris directly from a blood sample. |
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Carvalho, Â.; Ferreira, G.; Seixas, D.; Guimarães-Teixeira, C.; Henrique, R.; Monteiro, F.J.; Jerónimo, C. Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation. Cancers 2021, 13, 2101. https://doi.org/10.3390/cancers13092101
Carvalho Â, Ferreira G, Seixas D, Guimarães-Teixeira C, Henrique R, Monteiro FJ, Jerónimo C. Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation. Cancers. 2021; 13(9):2101. https://doi.org/10.3390/cancers13092101
Chicago/Turabian StyleCarvalho, Ângela, Gabriela Ferreira, Duarte Seixas, Catarina Guimarães-Teixeira, Rui Henrique, Fernando J. Monteiro, and Carmen Jerónimo. 2021. "Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation" Cancers 13, no. 9: 2101. https://doi.org/10.3390/cancers13092101