Recent advances of liquid biopsy: Interdisciplinary strategies toward clinical decision‐making

Deleted Journal, Journal Year: 2023, Volume and Issue: 1(4)

Published: Oct. 1, 2023

Abstract Liquid biopsy has emerged as a promising avenue for non‐invasive and rapid retrieval of pathological information from patient body fluids. Over the years, liquid garnered significant attention clinically treating cancer by selecting appropriate biomarkers such circulating tumor cells (CTCs) extracellular vesicles (EVs). Further integration advanced technologies facilitated efficient capture biopsy, revolutionizing clinical decision‐making in multiple processes stages patients. Underscoring intersection different disciplines, this review provides holistic summary recent breakthroughs specifically designed application distinctive to blend real‐world with material science. Firstly, we focus on main principles that facilitate release (e.g., CTCs EVs), leveraging their physicochemical properties. Then, applications are summarized, highlighting potential providing comprehensive information. Later, incorporation machine learning is also emphasized enhancing enabling deeper insights design next‐generation platforms specific biomarker isolation. Finally, future opportunities explored combining nanotechnologies artificial intelligence, thereby offering inconceivable possibilities improving care.

Language: Английский

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Whole-genome Mutational Analysis for Tumor-informed Detection of Circulating Tumor DNA in Patients with Urothelial Carcinoma

European Urology, Journal Year: 2024, Volume and Issue: 86(4), P. 301 - 311

Published: May 29, 2024

Circulating tumor DNA (ctDNA) can be used for sensitive detection of minimal residual disease (MRD). However, the probability detecting ctDNA in settings low burden is limited by number mutations analyzed and plasma volume available. We a whole-genome sequencing (WGS) approach patients with urothelial carcinoma.

Language: Английский

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Circulating tumour DNA in early stage and locally advanced NSCLC: ready for clinical implementation?

Nature Reviews Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

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Critical Factors in the Analytical Work Flow of Circulating Tumor DNA-Based Molecular Profiling

Clinical Chemistry, Journal Year: 2024, Volume and Issue: 70(1), P. 220 - 233

Published: Jan. 1, 2024

Abstract Background Liquid biopsy testing, especially molecular tumor profiling of circulating DNA (ctDNA) in cell-free plasma, has received increasing interest recent years as it serves a reliable alternative for the detection tumor-specific aberrations to guide treatment decision-making oncology. Many (commercially available) applications have been developed, however, broad divergences (pre)analytical work flows and lack universally applied guidelines impede routine clinical implementation. In this review, critical factors blood-based ctDNA liquid flow are evaluated. Content preanalytical phase, several aspects (e.g., blood collection tubes [BCTs], plasma processing, extraction method) affect quantity quality (ccfDNA) applicable subsequent analyses should meet certain standards be diagnostic flows. Analytical considerations, such analytical input choice assay, might vary based on application (i.e., screening, primary diagnosis, minimal residual disease [MRD], response monitoring, resistance identification). addition practical procedures, variant interpretation reporting results harmonized. Collaborative efforts (inter)national consortia societies essential establishment standard operating procedures (SOPs) attempts standardize plasma-based analysis flow. Summary Development regarding testing necessary pave way implementation diagnostics.

Language: Английский

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Liquid biopsy guides successful molecular targeted therapy of an inoperable pediatric brainstem neoplasm

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: Feb. 22, 2024

Abstract Midline CNS tumors are occasionally inaccessible for surgical biopsies. In these instances, cell-free DNA (cfDNA) may serve as a viable alternative molecular analysis and identification of targetable mutations. Here, we report young child with an inoperable brainstem tumor in whom stereotactic biopsy was deemed unsafe. The progressed on steroids after radiotherapy the patient developed hydrocephalus received ventriculoperitoneal shunt. Droplet digital PCR cfDNA from intraoperative cerebrospinal fluid liquid revealed BRAF V600 mutation enabling targeted treatment MEK inhibitors. patient, now trametinib dabrafenib 1 year, has had substantial volume regression reduction contrast enhancement MRIs is making remarkable clinical progress. This case highlights that subset tumors, access to be crucial identify actionable therapeutic targets would otherwise go undiscovered.

Language: Английский

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Systematically Evaluating Cell‐Free DNA Fragmentation Patterns for Cancer Diagnosis and Enhanced Cancer Detection via Integrating Multiple Fragmentation Patterns

Advanced Science, Journal Year: 2024, Volume and Issue: 11(30)

Published: June 17, 2024

Cell-free DNA (cfDNA) fragmentation patterns have immense potential for early cancer detection. However, the definition of varies, ranging from entire genome to specific genomic regions. These not been systematically compared, impeding broader research and practical implementation. Here, 1382 plasma cfDNA sequencing samples 8 types are collected. Considering that within open chromatin regions is more susceptible fragmentation, 10 as features employed machine learning techniques evaluate their performance examined. All demonstrated discernible classification capabilities, with end motif showing highest diagnostic value cross-validation. Combining cross independent validation results revealed incorporated both fragment length coverage information exhibited robust predictive capacities. Despite potential, power these unstable. To address this limitation, an ensemble classifier via integrating all developed, which notable improvements in detection tissue-of-origin determination. Further functional bioinformatics investigations on significant feature intervals model its impressive ability identify critical regulatory involved pathogenesis.

Language: Английский

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A perspective review on the systematic implementation of ctDNA in phase I clinical trial drug development

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: March 1, 2025

Abstract Circulating tumour DNA (ctDNA) represents an increasingly important biomarker for the screening, diagnosis and management of patients in clinical practice advanced/metastatic disease across multiple cancer types. In this context, ctDNA-based comprehensive genomic profiling is now available patient decisions, several companion diagnostic assays have been approved by regulatory agencies. However, although assessment ctDNA levels Phase II-III drug development gathering momentum, it remains somewhat surprisingly limited early I phases light potential opportunities provided such analysis. perspective review, we investigate hurdles applying testing inclusion monitoring phase 1 trials. This will enable more informed decisions regarding inclusion, dose optimization, proof-of-mechanism biological activity molecular response, thereby supporting evolving oncology paradigm. Furthermore, highlight use cost-efficient, agnostic genome-wide techniques (such as low-pass whole genome sequencing fragmentomics) methylation-based methods to facilitate a systematic integration trial settings.

Language: Английский

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Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Oct. 11, 2023

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published date demanded a very high-depth sequencing, resulting an elevated price test. Herein, we developed multimodal assay called SPOT-MAS (screening presence by methylation size) simultaneously profile methylomics, fragmentomics, copy number, end motifs single workflow using targeted shallow genome-wide sequencing (~0.55×) cell-free DNA. We applied 738 non-metastatic patients with breast, colorectal, gastric, lung, liver cancer, 1550 healthy controls. then employed machine learning extract multiple cancer tissue-specific signatures detecting locating cancer. successfully detected five types sensitivity 72.4% at 97.0% specificity. The sensitivities early-stage cancers were 73.9% 62.3% stages I II, respectively, increasing 88.3% stage IIIA. For tumor-of-origin, our achieved accuracy 0.7. Our study demonstrates comparable performance other ctDNA-based while requiring significantly lower depth, making it economically feasible population-wide screening.

Language: Английский

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Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 25, 2023

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published date demanded a very high-depth sequencing, resulting an elevated price test. Herein, we developed multimodal assay called SPOT-MAS (screening presence by methylation size) simultaneously profile methylomics, fragmentomics, copy number, end motifs single workflow using targeted shallow genome-wide sequencing (~0.55×) cell-free DNA. We applied 738 non-metastatic patients with breast, colorectal, gastric, lung, liver cancer, 1550 healthy controls. then employed machine learning extract multiple cancer tissue-specific signatures detecting locating cancer. successfully detected five types sensitivity 72.4% at 97.0% specificity. The sensitivities early-stage cancers were 73.9% 62.3% stages I II, respectively, increasing 88.3% stage IIIA. For tumor-of-origin, our achieved accuracy 0.7. Our study demonstrates comparable performance other ctDNA-based while requiring significantly lower depth, making it economically feasible population-wide screening.

Language: Английский

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Surpassing sensitivity limits in liquid biopsy

Science, Journal Year: 2024, Volume and Issue: 383(6680), P. 260 - 261

Published: Jan. 18, 2024

Attenuation of cell-free DNA clearance in vivo is an alternative strategy to maximize recovery.

Language: Английский

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