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Cancers
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Liquid Biopsy for Lung Cancer Treatment
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Liquid Biopsy for Lung Cancer Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: 30 July 2024 | Viewed by 15693

Special Issue Editors

Dr. Maria Palmieri

E-Mail Website
Guest Editor
Department of Medical Biotechnologies, University of Siena, Siena, Italy
Interests: functional genetic elements associated with cancers through liquid biopsy studies
Dr. Frullanti Elisa

E-Mail Website
Guest Editor
Department of Medical Biotechnologies, University of Siena, Siena, Italy
Interests: cancer genetics; tumor progression; deep-next generation sequencing; liquid biopsy; circulating tumor DNA; personalized therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the scientific efforts of recent years, the gold standard for lung cancer diagnosis is still based on radiological imaging followed by surgical tissue biopsy. However, the resulting information is a limited snapshot in space and time, poorly reflecting clonal heterogeneity or tumor evolution and metastasis. Over a decade since its inception, liquid biopsy is transforming the vision of cancer treatment. This non-invasive method makes it possible to analyze tumor biomarkers over time, allowing a better experience for the patient and paving the way for precision and personalized medicine.

We are pleased to invite you to contribute to the drafting of scientific work which will be published in Cancers (ISSN 2072-6694; Impact Factor 6.639), which will help to address the current need for early diagnosis in lung cancer patients. The Special Issue aims to identify innovative, non-invasive and effective strategies to detect lung cancers at an early stage, and to monitor the progression of the disease over time, allowing timely and targeted treatments for patients.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: cancers, lung cancers, cancer genetics, innovative technologies, and new strategies.

I look forward to receiving your contributions.

Dr. Maria Palmieri
Dr. Frullanti Elisa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • lung cancer
  • new strategies
  • liquid biopsy
  • CTC
  • exosomes
  • cf-NA
  • ddPCR
  • NGS

Published Papers (7 papers)

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Research

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16 pages, 2199 KiB  
Article
A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study)
by Yvonne L. E. Ang, Xiaotian Zhao, Thanyanan Reungwetwattana, Byoung-Chul Cho, Bin-Chi Liao, Rebecca Yeung, Herbert H. Loong, Dong-Wan Kim, James Chih-Hsin Yang, Sun Min Lim, Myung-Ju Ahn, Se-Hoon Lee, Thitiporn Suwatanapongched, Kanchaporn Kongchauy, Qiuxiang Ou, Ruoying Yu, Bee Choo Tai, Boon Cher Goh, Tony S. K. Mok and Ross A. Soo
Cancers 2023, 15(20), 4999; https://doi.org/10.3390/cancers15204999 - 16 Oct 2023
Cited by 2 | Viewed by 1911
Abstract
Epidermal growth factor receptor (EGFR) T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard [...] Read more.
Epidermal growth factor receptor (EGFR) T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA). PLASMA is a prospective, open-label, multicentre single-arm Phase II study. Patients with advanced NSCLC harbouring sensitizing EGFR and T790M mutations in plasma at progression from ≥one 1G/2G TKI were treated with 80 mg of Osimertinib daily until progression. The primary endpoint was the objective response rate (ORR); the secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicities. Plasma next-generation sequencing was performed to determine Osimertinib resistance mechanisms and assess serial ctDNA. A total of 110 patients from eight centres in five countries were enrolled from 2017 to 2019. The median follow-up duration was 2.64 (IQR 2.44–3.12) years. The ORR was 50.9% (95% CI 41.2–60.6) and the DCR was 84.5% (95% CI 76.4–90.7). Median PFS was 7.4 (95% CI 6.0–9.3) months; median OS was 1.63 (95% CI 1.35–2.16) years. Of all of the patients, 76% had treatment-related adverse events (TRAEs), most commonly paronychia (22.7%); 11% experienced ≥ Grade 3 TRAEs. The ctDNA baseline load and dynamics were prognostic. Osimertinib is active in NSCLC harbouring sensitizing EGFR and T790M mutations in ctDNA testing post 1G/2G TKIs. Full article
(This article belongs to the Special Issue Liquid Biopsy for Lung Cancer Treatment)
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11 pages, 1205 KiB  
Article
Monitoring of Plasma EGFR Mutations during Osimertinib Treatment for NSCLC Patients with Acquired T790M Mutation
by Kana Watanabe, Ryota Saito, Eisaku Miyauchi, Hiromi Nagashima, Atsushi Nakamura, Shunichi Sugawara, Nobuyuki Tanaka, Hiroshi Terasaki, Tatsuro Fukuhara and Makoto Maemondo
Cancers 2023, 15(17), 4231; https://doi.org/10.3390/cancers15174231 - 24 Aug 2023
Cited by 3 | Viewed by 1108
Abstract
Background: Osimertinib was first approved for the treatment of non-small cell lung cancer (NSCLC) in patients who have developed the epidermal growth factor receptor (EGFR) T790M mutation after treatment with EGFR tyrosine kinase inhibitors (TKIs). We routinely evaluated the plasma of NSCLC patients [...] Read more.
Background: Osimertinib was first approved for the treatment of non-small cell lung cancer (NSCLC) in patients who have developed the epidermal growth factor receptor (EGFR) T790M mutation after treatment with EGFR tyrosine kinase inhibitors (TKIs). We routinely evaluated the plasma of NSCLC patients with the T790M mutation to more rapidly detect an increase in disease activity and resistance to treatment. Methods: Eligible patients received osimertinib after resistance to the first- or second-generation of EGFR-TKIs in NSCLC harboring T790M mutation detectable in tumor tissue or plasma. Plasma samples were collected every 8 weeks during osimertinib treatment. The plasma analysis was performed using an improved PNA-LNA PCR clamp method. We tested samples for a resistance mechanism, including EGFR-activating, T790M, and C797S mutations, and assessed the association between the mutations and osimertinib treatment. Results: Of the 60 patients enrolled in the study, 58 were eligible for this analysis. In plasma collected before osimertinib treatment, activating mutations were detected in 47 of 58 patients (81.0%) and T790M was detected in 44 patients (75.9%). Activating mutations were cleared in 60.9% (28/46) and T790M was cleared in 93.0% (40/43). Of these, 71.4% (20/28) of activating mutations and 87.5% (35/40) of T790M mutation were cleared within 8 weeks of treatment. The total response rate (RR) was 53.4% (31/58). The median duration of treatment was 259 days, with a trend toward longer treatment duration in patients who experienced the clearance of activating mutations with osimertinib. At the time of disease progression during osimertinib treatment, C797S was detected in 3 of 37 patients (8.1%). Conclusion: Plasma EGFR mutation analysis was effective in predicting the effect of osimertinib treatment. Full article
(This article belongs to the Special Issue Liquid Biopsy for Lung Cancer Treatment)
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Review

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14 pages, 691 KiB  
Review
ctDNA for the Evaluation and Management of EGFR-Mutant Non-Small Cell Lung Cancer
by Aakash Desai, Tadana A. Vázquez, Keishla M. Arce, Marcelo Corassa, Philip C. Mack, Jhanelle E. Gray and Bruna Pellini
Cancers 2024, 16(5), 940; https://doi.org/10.3390/cancers16050940 - 26 Feb 2024
Viewed by 2156
Abstract
Circulating tumor DNA (ctDNA) offers a new paradigm in optimizing treatment strategies for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Its potential spans early-stage disease, influencing adjuvant therapy, to advanced disease, where it aids in identifying genomic markers and [...] Read more.
Circulating tumor DNA (ctDNA) offers a new paradigm in optimizing treatment strategies for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Its potential spans early-stage disease, influencing adjuvant therapy, to advanced disease, where it aids in identifying genomic markers and resistance mechanisms. This review explores the evolving landscape of utilizing liquid biopsies, specifically circulating tumor DNA (ctDNA), in the management of NSCLC with EGFR mutations. While tissue-based genomic testing remains the cornerstone for clinical decision-making, liquid biopsies offer a well-validated, guideline-recommended alternative approach. Ongoing trials integrating ctDNA for EGFR-mutant NSCLC management are also discussed, shedding light on the potential of ctDNA in early-stage disease, including its applications in prognostication, risk stratification, and minimal residual disease detection post-curative intent treatment. For advanced disease, the role of ctDNA in identifying resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs) is explored, providing insights into disease progression and guiding treatment decisions. This review also addresses the challenges, including the limitations in sensitivity of current assays for disease recurrence detection, and calls for future studies to refine treatment approaches, standardize reporting, and explore alternative biofluids for enhanced sensitivity. A systematic approach is crucial to address barriers to ctDNA deployment, ensuring equitable access, and facilitating its integration into routine clinical practice. Full article
(This article belongs to the Special Issue Liquid Biopsy for Lung Cancer Treatment)
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49 pages, 6076 KiB  
Review
Emerging Biosensing Methods to Monitor Lung Cancer Biomarkers in Biological Samples: A Comprehensive Review
by Raja Chinnappan, Tanveer Ahmad Mir, Sulaiman Alsalameh, Tariq Makhzoum, Alaa Alzhrani, Khalid Alnajjar, Salma Adeeb, Noor Al Eman, Zara Ahmed, Ismail Shakir, Khaled Al-Kattan and Ahmed Yaqinuddin
Cancers 2023, 15(13), 3414; https://doi.org/10.3390/cancers15133414 - 29 Jun 2023
Cited by 4 | Viewed by 2235
Abstract
Lung cancer is the most commonly diagnosed of all cancers and one of the leading causes of cancer deaths among men and women worldwide, causing 1.5 million deaths every year. Despite developments in cancer treatment technologies and new pharmaceutical products, high mortality and [...] Read more.
Lung cancer is the most commonly diagnosed of all cancers and one of the leading causes of cancer deaths among men and women worldwide, causing 1.5 million deaths every year. Despite developments in cancer treatment technologies and new pharmaceutical products, high mortality and morbidity remain major challenges for researchers. More than 75% of lung cancer patients are diagnosed in advanced stages, leading to poor prognosis. Lung cancer is a multistep process associated with genetic and epigenetic abnormalities. Rapid, accurate, precise, and reliable detection of lung cancer biomarkers in biological fluids is essential for risk assessment for a given individual and mortality reduction. Traditional diagnostic tools are not sensitive enough to detect and diagnose lung cancer in the early stages. Therefore, the development of novel bioanalytical methods for early-stage screening and diagnosis is extremely important. Recently, biosensors have gained tremendous attention as an alternative to conventional methods because of their robustness, high sensitivity, inexpensiveness, and easy handling and deployment in point-of-care testing. This review provides an overview of the conventional methods currently used for lung cancer screening, classification, diagnosis, and prognosis, providing updates on research and developments in biosensor technology for the detection of lung cancer biomarkers in biological samples. Finally, it comments on recent advances and potential future challenges in the field of biosensors in the context of lung cancer diagnosis and point-of-care applications. Full article
(This article belongs to the Special Issue Liquid Biopsy for Lung Cancer Treatment)
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12 pages, 715 KiB  
Review
Liquid Biopsy in Early-Stage Lung Cancer: Current and Future Clinical Applications
by Olivia Vandekerckhove, Kristof Cuppens, Karin Pat, Bert Du Pont, Guy Froyen and Brigitte Maes
Cancers 2023, 15(10), 2702; https://doi.org/10.3390/cancers15102702 - 10 May 2023
Cited by 3 | Viewed by 2322
Abstract
Lung cancer remains the leading cause of cancer death worldwide, with the majority of cases diagnosed in an advanced stage. Early-stage disease non-small cell lung cancer (NSCLC) has a better outcome, nevertheless the 5-year survival rates drop from 60% for stage IIA to [...] Read more.
Lung cancer remains the leading cause of cancer death worldwide, with the majority of cases diagnosed in an advanced stage. Early-stage disease non-small cell lung cancer (NSCLC) has a better outcome, nevertheless the 5-year survival rates drop from 60% for stage IIA to 36% for stage IIIA disease. Early detection and optimized perioperative systemic treatment are frontrunner strategies to reduce this burden. The rapid advancements in molecular diagnostics as well as the growing availability of targeted therapies call for the most efficient detection of actionable biomarkers. Liquid biopsies have already proven their added value in the management of advanced NSCLC but can also optimize patient care in early-stage NSCLC. In addition to having known diagnostic benefits of speed, accessibility, and enhanced biomarker detection compared to tissue biopsy, liquid biopsy could be implemented for screening, diagnostic, and prognostic purposes. Furthermore, liquid biopsy can optimize therapeutic management by overcoming the issue of tumor heterogeneity, monitoring tumor burden, and detecting minimal residual disease (MRD), i.e., the presence of tumor-specific ctDNA, post-operatively. The latter is strongly prognostic and is likely to become a guidance in the postsurgical management. In this review, we present the current evidence on the clinical utility of liquid biopsy in early-stage lung cancer, discuss a selection of key trials, and suggest future applications. Full article
(This article belongs to the Special Issue Liquid Biopsy for Lung Cancer Treatment)
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27 pages, 872 KiB  
Review
Sequence-Based Platforms for Discovering Biomarkers in Liquid Biopsy of Non-Small-Cell Lung Cancer
by Liam J. Brockley, Vanessa G. P. Souza, Aisling Forder, Michelle E. Pewarchuk, Melis Erkan, Nikita Telkar, Katya Benard, Jessica Trejo, Matt D. Stewart, Greg L. Stewart, Patricia P. Reis, Wan L. Lam and Victor D. Martinez
Cancers 2023, 15(8), 2275; https://doi.org/10.3390/cancers15082275 - 13 Apr 2023
Cited by 4 | Viewed by 3387
Abstract
Lung cancer detection and monitoring are hampered by a lack of sensitive biomarkers, which results in diagnosis at late stages and difficulty in tracking response to treatment. Recent developments have established liquid biopsies as promising non-invasive methods for detecting biomarkers in lung cancer [...] Read more.
Lung cancer detection and monitoring are hampered by a lack of sensitive biomarkers, which results in diagnosis at late stages and difficulty in tracking response to treatment. Recent developments have established liquid biopsies as promising non-invasive methods for detecting biomarkers in lung cancer patients. With concurrent advances in high-throughput sequencing technologies and bioinformatics tools, new approaches for biomarker discovery have emerged. In this article, we survey established and emerging biomarker discovery methods using nucleic acid materials derived from bodily fluids in the context of lung cancer. We introduce nucleic acid biomarkers extracted from liquid biopsies and outline biological sources and methods of isolation. We discuss next-generation sequencing (NGS) platforms commonly used to identify novel biomarkers and describe how these have been applied to liquid biopsy. We highlight emerging biomarker discovery methods, including applications of long-read sequencing, fragmentomics, whole-genome amplification methods for single-cell analysis, and whole-genome methylation assays. Finally, we discuss advanced bioinformatics tools, describing methods for processing NGS data, as well as recently developed software tailored for liquid biopsy biomarker detection, which holds promise for early diagnosis of lung cancer. Full article
(This article belongs to the Special Issue Liquid Biopsy for Lung Cancer Treatment)
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Other

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18 pages, 1538 KiB  
Systematic Review
Circulating Tumour DNA (ctDNA) as a Predictor of Clinical Outcome in Non-Small Cell Lung Cancer Undergoing Targeted Therapies: A Systematic Review and Meta-Analysis
by Farzana Y. Zaman, Ashwin Subramaniam, Afsana Afroz, Zarka Samoon, Daniel Gough, Surein Arulananda and Muhammad Alamgeer
Cancers 2023, 15(9), 2425; https://doi.org/10.3390/cancers15092425 - 23 Apr 2023
Cited by 6 | Viewed by 1711
Abstract
Background: Liquid biopsy (LB) analysis using (ctDNA)/cell-free DNA (cfDNA) is an emerging alternative to tissue profiling in (NSCLC). LB is used to guide treatment decisions, detect resistance mechanisms, and predicts responses, and, therefore, outcomes. This systematic review and meta-analysis evaluated the impact of [...] Read more.
Background: Liquid biopsy (LB) analysis using (ctDNA)/cell-free DNA (cfDNA) is an emerging alternative to tissue profiling in (NSCLC). LB is used to guide treatment decisions, detect resistance mechanisms, and predicts responses, and, therefore, outcomes. This systematic review and meta-analysis evaluated the impact of LB quantification on clinical outcomes in molecularly altered advanced NSCLC undergoing targeted therapies. Methods: We searched Embase, MEDLINE, PubMed, and Cochrane Database, between 1 January 2020 and 31 August 2022. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rate (ORR), sensitivity, and specificity. Age stratification was performed based on the mean age of the individual study population. The quality of studies was assessed using the Newcastle–Ottawa Scale (NOS). Results: A total of 27 studies (3419 patients) were included in the analysis. Association of baseline ctDNA with PFS was reported in 11 studies (1359 patients), while that of dynamic changes with PFS was reported in 16 studies (1659 patients). Baseline ctDNA-negative patients had a trend towards improved PFS (pooled hazard ratio [pHR] = 1.35; 95%CI: 0.83–1.87; p < 0.001; I2 = 96%) than ctDNA-positive patients. Early reduction/clearance of ctDNA levels after treatment was related to improved PFS (pHR = 2.71; 95%CI: 1.85–3.65; I2 = 89.4%) compared to those with no reduction/persistence in ctDNA levels. The sensitivity analysis based on study quality (NOS) demonstrated improved PFS only for good [pHR = 1.95; 95%CI: 1.52–2.38] and fair [pHR = 1.99; 95%CI: 1.09–2.89] quality studies, but not for poor quality studies. There was, however, a high level of heterogeneity (I2 = 89.4%) along with significant publication bias in our analysis. Conclusions: This large systematic review, despite heterogeneity, found that baseline negative ctDNA levels and early reduction in ctDNA following treatment could be strong prognostic markers for PFS and OS in patients undergoing targeted therapies for advanced NSCLC. Future randomised clinical trials should incorporate serial ctDNA monitoring to further establish the clinical utility in advanced NSCLC management. Full article
(This article belongs to the Special Issue Liquid Biopsy for Lung Cancer Treatment)
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