Liquid Biopsy Using Methylation Sequencing for Lung Cancer

Background: The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or from the histologic transformation of non-small cell lung cancer (NSCLC). Methods: A systematic review of studies adopting LB in patients with SCLC have been performed to assess the clinical utility of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs). Results: After a screening of 728 records, 62 studies (32 evaluating CTCs, 27 ctDNA, and 3 both) met predetermined eligibility criteria. Only four studies evaluated LB in the diagnostic setting for SCLC, while its prognostic significance was evaluated in 38 studies and prominently supported by both ctDNA and CTCs. A meta-analysis of 11 studies as for CTCs enumeration showed an HR for overall survival of 2.63 (1.71–4.05), with a potential publication bias. The feasibility of tumor genomic profiling and the predictive role of LB in terms of response/resistance to chemotherapy was assessed in 11 and 24 studies, respectively, with greater consistency for those regarding ctDNA. Intriguingly, several case reports suggest that LB can indirectly capture the transition to SCLC in NSCLC treated with EGFR tyrosine kinase inhibitors. Conclusions: While dedicated trials are needed, LB holds potential clinical roles in both de novo and transformed SCLC. CtDNA analysis appears the most valuable and practicable tool for both disease monitoring and genomic profiling.

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Use of Liquid Biopsy in the Care of Patients with Non-Small Cell Lung Cancer

Current Treatment Options in Oncology ◽

10.1007/s11864-021-00882-9 ◽

2021 ◽

Vol 22 (10) ◽

Cited By ~ 1

Author(s):

Atocha Romero ◽

Roberto Serna-Blasco ◽

Virginia Calvo ◽

Mariano Provencio

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Liquid Biopsy ◽

Small Cell ◽

Small Cell Lung

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Mutated circulating tumor DNA as a liquid biopsy in lung cancer detection and treatment

Molecular Oncology ◽

10.1002/1878-0261.12983 ◽

2021 ◽

Author(s):

Martyna Filipska ◽

Rafael Rosell

Keyword(s):

Lung Cancer ◽

Cancer Detection ◽

Liquid Biopsy ◽

Circulating Tumor Dna ◽

Lung Cancer Detection ◽

Tumor Dna

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Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer

Biomedicines ◽

10.3390/biomedicines9010048 ◽

2021 ◽

Vol 9 (1) ◽

pp. 48

Author(s):

Patricia Mondelo-Macía ◽

Jorge García-González ◽

Luis León-Mateos ◽

Adrián Castillo-García ◽

Rafael López-López ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Liquid Biopsy ◽

Small Cell ◽

New Drugs ◽

Current Status ◽

Small Cell Lung ◽

Tumor Biopsy ◽

Future Utility

Approximately 19% of all cancer-related deaths are due to lung cancer, which is the leading cause of mortality worldwide. Small cell lung cancer (SCLC) affects approximately 15% of patients diagnosed with lung cancer. SCLC is characterized by aggressiveness; the majority of SCLC patients present with metastatic disease, and less than 5% of patients are alive at 5 years. The gold standard of SCLC treatment is platinum and etoposide-based chemotherapy; however, its effects are short. In recent years, treatment for SCLC has changed; new drugs have been approved, and new biomarkers are needed for treatment selection. Liquid biopsy is a non-invasive, rapid, repeated and alternative tool to the traditional tumor biopsy that could allow the most personalized medicine into the management of SCLC patients. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are the most commonly used liquid biopsy biomarkers. Some studies have reported the prognostic factors of CTCs and cfDNA in SCLC patients, independent of the stage. In this review, we summarize the recent SCLC studies of CTCs, cfDNA and other liquid biopsy biomarkers, and we discuss the future utility of liquid biopsy in the clinical management of SCLC.

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The Liquid Biopsy for Lung Cancer: State of the Art, Limitations and Future Developments

Cancers ◽

10.3390/cancers13163923 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3923

Author(s):

Daniel Di Capua ◽

Dara Bracken-Clarke ◽

Karine Ronan ◽

Anne-Marie Baird ◽

Stephen Finn

Keyword(s):

Lung Cancer ◽

Lung Carcinoma ◽

Targeted Therapies ◽

Liquid Biopsy ◽

Genetic Alterations ◽

Rapid Progression ◽

Liquid Biopsies ◽

Cell Lung Carcinoma ◽

Genetic Sequencing ◽

Tissue Biopsy

Lung cancer is a leading cause of cancer-related deaths, contributing to 18.4% of cancer deaths globally. Treatment of non-small cell lung carcinoma has seen rapid progression with targeted therapies tailored to specific genetic drivers. However, identifying genetic alterations can be difficult due to lack of tissue, inaccessible tumors and the risk of complications for the patient with serial tissue sampling. The liquid biopsy provides a minimally invasive method which can obtain circulating biomarkers shed from the tumor and could be a safer alternative to tissue biopsy. While tissue biopsy remains the gold standard, liquid biopsies could be very beneficial where serial sampling is required, such as monitoring disease progression or development of resistance mutations to current targeted therapies. Liquid biopsies also have a potential role in identifying patients at risk of relapse post treatment and as a component of future lung cancer screening protocols. Rapid developments have led to multiple platforms for isolating circulating tumor cells (CTCs) and detecting circulating tumor DNA (ctDNA); however, standardization is lacking, especially in lung carcinoma. Additionally, clonal hematopoiesis of uncertain clinical significance must be taken into consideration in genetic sequencing, as it introduces the potential for false positives. Various biomarkers have been investigated in liquid biopsies; however, in this review, we will concentrate on the current use of ctDNA and CTCs, focusing on the clinical relevance, current and possible future applications and limitations of each.

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Liquid Biopsy Analysis in Clinical Practice: Focus on Lung Cancer

Journal of Molecular Pathology ◽

10.3390/jmp2030021 ◽

2021 ◽

Vol 2 (3) ◽

pp. 241-254

Author(s):

Pasquale Pisapia ◽

Francesco Pepe ◽

Antonino Iaccarino ◽

Roberta Sgariglia ◽

Mariantonia Nacchio ◽

...

Keyword(s):

Lung Cancer ◽

Liquid Biopsy ◽

Treatment Options ◽

Molecular Testing ◽

Specific Information ◽

Sample Collection ◽

Timely Manner ◽

Oncology Practice ◽

Nsclc Patients ◽

To Receive

Lung cancer is the leading cause of cancer death worldwide. Despite the emergence of highly effective targeted therapies, up to 30% of advanced stage non-small cell lung cancer (NSCLC) patients do not undergo tissue molecular testing because of scarce tissue availability. Liquid biopsy, on the other hand, offers these patients a valuable opportunity to receive the best treatment options in a timely manner. Indeed, besides being much faster and less invasive than conventional tissue-based analysis, it can also yield specific information about the genetic make-up and evolution of patients’ tumors. However, several issues, including lack of standardized protocols for sample collection, processing, and interpretation, still need to be addressed before liquid biopsy can be fully incorporated into routine oncology practice. Here, we reviewed the most important challenges hindering the implementation of liquid biopsy in oncology practice, as well as the great advantages of this approach for the treatment of NSCLC patients.

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Circulating Biomarkers of Response and Toxicity of Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Review

Cancers ◽

10.3390/cancers13081794 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1794

Author(s):

Alice Indini ◽

Erika Rijavec ◽

Francesco Grossi

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Liquid Biopsy ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Circulating Biomarkers ◽

Small Cell Lung ◽

Nsclc Patients

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to these agents. Furthermore, although immunotherapy is usually well tolerated, some patients experience severe immune-related adverse events (irAEs). Liquid biopsy is a non-invasive diagnostic procedure involving the isolation of circulating biomarkers, such as circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs). Thanks to recent advances in technologies, such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), liquid biopsy has become a useful tool to provide baseline information on the tumor, and to monitor response to treatments. This review highlights the potential role of liquid biomarkers in the selection of NSCLC patients who could respond to immunotherapy, and in the identification of patients who are most likely to experience irAEs, in order to guide improvements in care.

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Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation

Cancers ◽

10.3390/cancers13092101 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2101

Author(s):

Ângela Carvalho ◽

Gabriela Ferreira ◽

Duarte Seixas ◽

Catarina Guimarães-Teixeira ◽

Rui Henrique ◽

...

Keyword(s):

Lung Cancer ◽

Liquid Biopsy ◽

Residual Disease ◽

Lab On A Chip ◽

Microfluidic Devices ◽

Early Recurrence ◽

Circulating Tumor Dna ◽

Clinical Validation ◽

Liquid Biopsies ◽

Lung Cancer Patients

Despite the intensive efforts dedicated to cancer diagnosis and treatment, lung cancer (LCa) remains the leading cause of cancer-related mortality, worldwide. The poor survival rate among lung cancer patients commonly results from diagnosis at late-stage, limitations in characterizing tumor heterogeneity and the lack of non-invasive tools for detection of residual disease and early recurrence. Henceforth, research on liquid biopsies has been increasingly devoted to overcoming these major limitations and improving management of LCa patients. Liquid biopsy is an emerging field that has evolved significantly in recent years due its minimally invasive nature and potential to assess various disease biomarkers. Several strategies for characterization of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been developed. With the aim of standardizing diagnostic and follow-up practices, microfluidic devices have been introduced to improve biomarkers isolation efficiency and specificity. Nonetheless, implementation of lab-on-a-chip platforms in clinical practice may face some challenges, considering its recent application to liquid biopsies. In this review, recent advances and strategies for the use of liquid biopsies in LCa management are discussed, focusing on high-throughput microfluidic devices applied for CTCs and ctDNA isolation and detection, current clinical validation studies and potential clinical utility.

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Peptide-Affinity Precipitation of Extracellular Vesicles and Cell-Free DNA Improves Sequencing Performance for the Detection of Pathogenic Mutations in Lung Cancer Patient Plasma

International Journal of Molecular Sciences ◽

10.3390/ijms21239083 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9083

Author(s):

Catherine Taylor ◽

Simi Chacko ◽

Michelle Davey ◽

Jacynthe Lacroix ◽

Alexander MacPherson ◽

...

Keyword(s):

Lung Cancer ◽

Extracellular Vesicles ◽

Liquid Biopsy ◽

Nsclc Patient ◽

Egfr Mutations ◽

Single Nucleotide Variants ◽

Cell Free Dna ◽

Free Dna ◽

Nsclc Patients ◽

Peptide Affinity

Liquid biopsy is a minimally-invasive diagnostic method that may improve access to molecular profiling for non-small cell lung cancer (NSCLC) patients. Although cell-free DNA (cf-DNA) isolation from plasma is the standard liquid biopsy method for detecting DNA mutations in cancer patients, the sensitivity can be highly variable. Vn96 is a peptide with an affinity for both extracellular vesicles (EVs) and circulating cf-DNA. In this study, we evaluated whether peptide-affinity (PA) precipitation of EVs and cf-DNA from NSCLC patient plasma improves the sensitivity of single nucleotide variants (SNVs) detection and compared observed SNVs with those reported in the matched tissue biopsy. NSCLC patient plasma was subjected to either PA precipitation or cell-free methods and total nucleic acid (TNA) was extracted; SNVs were then detected by next-generation sequencing (NGS). PA led to increased recovery of DNA as well as an improvement in NGS sequencing parameters when compared to cf-TNA. Reduced concordance with tissue was observed in PA-TNA (62%) compared to cf-TNA (81%), mainly due to identification of SNVs in PA-TNA that were not observed in tissue. EGFR mutations were detected in PA-TNA with 83% sensitivity and 100% specificity. In conclusion, PA-TNA may improve the detection limits of low-abundance alleles using NGS.

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