From haystack to high precision: advanced sequencing methods to unraveling circulating tumor DNA mutations DOI Creative Commons

Tamires Ferreira da Silva,

Juscelino Carvalho de Azevedo, Eliel Barbosa Teixeira

и другие.

Frontiers in Molecular Biosciences, Год журнала: 2024, Номер 11

Опубликована: Авг. 6, 2024

Identifying mutations in cancer-associated genes to guide patient treatments is essential for precision medicine. Circulating tumor DNA (ctDNA) offers valuable insights early cancer detection, treatment assessment, and surveillance. However, a key issue ctDNA analysis from the bloodstream choice of technique with adequate sensitivity identify low frequent molecular changes. Next-generation sequencing (NGS) technology, evolving parallel long-read capabilities, enhances mutation analysis. In present review, we describe different NGS approaches identifying mutation, discussing challenges standardized methodologies, cost, specificity, clinical context, bioinformatics expertise optimal application.

Язык: Английский

Genomic approaches to cancer and minimal residual disease detection using circulating tumor DNA DOI Creative Commons
Nicholas P. Semenkovich, Jeffrey J. Szymanski, Noah Earland

и другие.

Journal for ImmunoTherapy of Cancer, Год журнала: 2023, Номер 11(6), С. e006284 - e006284

Опубликована: Июнь 1, 2023

Liquid biopsies using cell-free circulating tumor DNA (ctDNA) are being used frequently in both research and clinical settings. ctDNA can be to identify actionable mutations personalize systemic therapy, detect post-treatment minimal residual disease (MRD), predict responses immunotherapy. also isolated from a range of different biofluids, with the possibility detecting locoregional MRD increased sensitivity if sampling more proximally than blood plasma. However, detection remains challenging early-stage settings where levels minuscule giving high risk for false negative results, which is balanced positive results clonal hematopoiesis. To address these challenges, researchers have developed ever-more elegant approaches lower limit (LOD) assays toward part-per-million boost assay specificity by reducing sources low-level technical biological noise, harnessing specific genomic epigenomic features ctDNA. In this review, we highlight modern analysis, including advancements made improve signal-to-noise ratio. We further challenge ultra-rare tumor-associated variants, overcoming will open new frontier personalized adjuvant treatment decision-making.

Язык: Английский

Процитировано

35
Recent advances in lung cancer research: unravelling the future of treatment DOI
Luca Bertolaccini, Monica Casiraghi, Clarissa Uslenghi

и другие.

Updates in Surgery, Год журнала: 2024, Номер 76(6), С. 2129 - 2140

Опубликована: Апрель 6, 2024

Язык: Английский

Процитировано

14
Circulating tumor DNA methylation detection as biomarker and its application in tumor liquid biopsy: advances and challenges DOI Creative Commons
Lingyu Li, Yingli Sun

MedComm, Год журнала: 2024, Номер 5(11)

Опубликована: Ноя. 1, 2024

Abstract Circulating tumor DNA (ctDNA) methylation, an innovative liquid biopsy biomarker, has emerged as a promising tool in early cancer diagnosis, monitoring, and prognosis prediction. As noninvasive approach, overcomes the limitations of traditional tissue biopsy. Among various biomarkers, ctDNA methylation garnered significant attention due to its high specificity detection capability across diverse types. Despite immense potential, clinical application faces substantial challenges pertaining sensitivity, specificity, standardization. In this review, we begin by introducing basic biology common techniques methylation. We then explore recent advancements faced biopsies. This includes progress screening identification molecular subtypes, monitoring recurrence minimal residual disease (MRD), prediction treatment response prognosis, assessment burden, determination origin. Finally, discuss future perspectives applications. comprehensive overview underscores vital role enhancing diagnostic accuracy, personalizing treatments, effectively progression, providing valuable insights for research practice.

Язык: Английский

Процитировано

10
The hype around ctDNA guiding an informed perioperative therapeutic strategy in early-stage non-small cell lung cancer DOI Creative Commons
Gaia Passarella, Stefania Canova,

Maria Ida Abbate

и другие.

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 29, 2025

Non-small cell lung cancer (NSCLC) remains a dire disease being the first cause of death among both genders. Early-stage NSCLC often has better treatment outcomes despite it highly heterogeneous disease. So far, neo-adjuvant chemotherapy strategies have led to small benefit with an improvement 5% in overall survival as absolute benefit. Recently, introduction immune checkpoint inhibitors combined shown robust efficacy terms event-free and survival. Thus, these combinations are today considered new standard care early-stage NSCLC. The application all-comer population lead confounding definitive results regarding predictive biomarkers urgently needed balancing promise healing than toxicities. At present, clinical staging TNM system guides choice, however is not entirely sufficient. Circulant tumoral DNA (ctDNA) emerged promising prognostic biomarker that may guide future perioperative strategy pave way personalized medicine also this exciting field. This narrative review aims put context employment ctDNA, give some perspective suggestions weighing pros cons technique for our tomorrow practice.

Язык: Английский

Процитировано

1
Prospective Evaluation of Circulating Tumor DNA using Next Generation Sequencing as a Biomarker during Neoadjuvant Chemotherapy in Localized Pancreatic Cancer DOI
Dhavan Shah, Amy Wells, M.C. Cox

и другие.

Annals of Surgery, Год журнала: 2024, Номер unknown

Опубликована: Янв. 23, 2024

Objective: In this prospective study, we aim to characterize the prognostic value of circulating tumor DNA (ctDNA) by next-generation-sequencing (NGS) in patients undergoing neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC). Summary Background Data: Circulating is a promising blood-based biomarker that several malignancies. Detection ctDNA NGS may provide insights regarding mutational profiles PDAC help guide clinical decisions potentially curative setting. However, utility as localized remains unclear. Methods: Patients with were enrolled study at Northwestern Medicine between October 2020 and 2022. Blood samples collected perform targeted agnostic utilizing Tempus x|F 105 gene panel three timepoints: pre-therapy (at diagnosis), post-NAC, after local therapy, including surgery. The relationship detection CA19-9, significance analyzed. Results: 56 included analysis. was detectable 48% diagnosis, 33% 41% therapy. After completion NAC, had higher CA19-9 levels versus those without (78.4 vs. 30.0, P =0.02). presence baseline associated response; significant response following NAC (109.0 U/mL 31.5 U/mL; =0.01), while present diagnosis did not (198.1 113.8 =0.77). treated KRAS independently predicted worse progression-free-survival. Conclusion: This report demonstrates analysis PDAC. treatment NAC. predicts survival

Язык: Английский

Процитировано

8
Circulating tumor DNA methylation: a promising clinical tool for cancer diagnosis and management DOI Creative Commons
Binliang Wang, Meng Wang,

Ya Lin

и другие.

Clinical Chemistry and Laboratory Medicine (CCLM), Год журнала: 2024, Номер 62(11), С. 2111 - 2127

Опубликована: Март 5, 2024

Cancer continues to pose significant challenges the medical community. Early detection, accurate molecular profiling, and adequate assessment of treatment response are critical factors in improving quality life survival cancer patients. Accumulating evidence shows that circulating tumor DNA (ctDNA) shed by tumors into peripheral blood preserves genetic epigenetic information primary tumors. Notably, methylation, an essential stable modification, exhibits both cancer- tissue-specific patterns. As a result, ctDNA methylation has emerged as promising marker for noninvasive testing clinics. In this review, we summarize existing techniques describe current research status present potential applications ctDNA-based assays clinic. The insights presented article could serve roadmap future clinical methylation.

Язык: Английский

Процитировано

7
Diagnostics of lung cancer by fragmentated blood circulating cell-free DNA based on machine learning methods DOI Creative Commons
Ivan O. Meshkov,

Alexander P. Koturgin,

П. В. Ершов

и другие.

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Янв. 29, 2025

Introduction Minimally invasive diagnostics based on liquid biopsy makes it possible early detection of lung cancer (LC). The blood plasma circulating cell-free DNA (cfDNA) fragments reflect the genome and chromatin status are considered as integral biomarkers biological entities for ‘cancer-of-origin’ prediction. aim this work is to create a method processing next-generation sequencing (NGS) data an interpretable binary classification model (CM), which analyzed cfDNA fragmentation features distinguishing healthy subjects with LC. Methods 148 138 LC were included in study. fractions, isolated from biospecimens, used libraries preparations NGS NovaSeq 6,000 Illumina system coverage 100 million reads/sample. Twelve variables, describing abundance length distribution within each genomic interval, 40 variables values position-weight matrices, combinations 5-bp-long terminal motifs fragments, characterize fragmentation. Classification models first phase machine learning either logistic regression L1- L2-regularization or probabilistic CMs Gaussian processes. second CM was kernel regression. Results final can distinguish AUC 0.872–0.875. performance developed evaluated using datum testing sets stage category. Sensitivity ranged 66.7 85.7%, 77.8 100%, 70 80% stages I, II, III, respectively. Specificity 79.3 90.0%. Discussion Thus, has good diagnostic value does not require clinical other tumor-associated biomarkers. current some advantages future implementation decision-making support due requires exclusively NGS-analysis fragmentation; accuracy depend any additional data; highly traceable; appropriate modular architecture.

Язык: Английский

Процитировано

1
Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis DOI Creative Commons
Lingfeng Bi, Xin Wang, Jiayi Li

и другие.

MedComm, Год журнала: 2025, Номер 6(3)

Опубликована: Фев. 21, 2025

Abstract The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, noncoding RNA changes, often precede genetic mutations are critical in progression. In this study, we explore how biopsy, combined markers, can provide cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges targeting regulators, which could disrupt cellular balance if overexploited, need maintaining key gene expressions therapeutic applications. This review highlights promise using early‐stage diagnosis, a focus on optimizing treatment strategies precision medicine.

Язык: Английский

Процитировано

1
Functional tumor-derived exosomes in NSCLC progression and clinical implications DOI Creative Commons
Yuxin Gao, Jun Xie,

Zhenya Yang

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 19, 2025

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases and remains one the leading causes cancer-related mortality worldwide. The high rate is primarily driven by delayed diagnosis, rapid metastasis, frequent recurrence. Tumor-derived exosomes (TEXs) have emerged as critical mediators in NSCLC progression, offering valuable insights into tumor microenvironment. Exosomes are small membrane vesicles that facilitate intercellular communication transport bioactive molecules, including proteins, RNAs, DNAs, thereby reflecting genetic complexity tumors. These play a key role promoting epithelial-mesenchymal transition (EMT), neovascularization, drug resistance, immune evasion, which pivotal development NSCLC. This review explores diverse roles TEXs focusing on their involvement pre-metastatic niche formation, tissue modulation. Specifically, we discuss exosome-associated RNAs proteins NSCLC, contribute to growth metastasis. Furthermore, explore potential biomarkers emphasizing application prognosis, prediction resistance targeted therapies immunotherapies.

Язык: Английский

Процитировано

1
Current and future therapies for small cell lung carcinoma DOI Creative Commons
Xiaoqian Zhai, Zhengkun Zhang, Yuxin Chen

и другие.

Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)

Опубликована: Апрель 1, 2025

Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid proliferation and high metastatic potential. It universal inactivation of RB1, overexpression the MYC family dysregulation multiple oncogenic signaling pathways. Among different patients, SCLCs are similar at genetic level but exhibit significant heterogeneity molecular level. The classification SCLC has evolved from a simple neuroendocrine (NE)/non-neuroendocrine (non-NE) system to transcription factor-based subtype system; lineage plasticity adds further complexity poses challenges for therapeutic development. While initially sensitive platinum-based chemotherapy, resistance develops rapidly, leading dismal prognosis. Various antibodies, including PD-1/PD-L1 inhibitors antibody‒drug conjugates, have been introduced into clinical practice or being evaluated in trials. However, their benefits patients remain limited. This review summarizes carcinogenic mechanisms, tumor heterogeneity, immune microenvironment SCLC, with focus on recent advances metastasis mechanisms. Additionally, corresponding progress tackling these discussed.

Язык: Английский

Процитировано

1