EMBO Molecular Medicine, Год журнала: 2024, Номер 16(9), С. 2188 - 2209
Опубликована: Авг. 20, 2024
Язык: Английский
Nature Medicine, Год журнала: 2024, Номер 30(4), С. 1023 - 1034
Опубликована: Март 19, 2024
Abstract Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity dual programmed cell death protein 1 (PD-1) lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab–relatlimab B, in combination chemoradiotherapy 32 patients resectable stage II/stage III gastroesophageal together an in-depth evaluation pathological, molecular functional responses. Primary endpoint was safety; the secondary feasibility; exploratory endpoints included pathological complete (pCR) major response (MPR), recurrence-free survival (RFS) overall (OS). The study met its primary safety Arm although B required modification to mitigate toxicity. pCR MPR rates were 40% 53.5% A 21.4% 57.1% B. Most common adverse events fatigue, nausea, thrombocytopenia dermatitis. Overall, 2-year RFS OS 72.5% 82.6%, respectively. Higher baseline ligand (PD-L1) LAG-3 expression associated deeper Exploratory analyses circulating tumor DNA (ctDNA) showed undetectable ctDNA post-ICI induction, preoperatively postoperatively had significantly longer OS; clearance reflective neoantigen-specific T Our findings provide insights into profile combined PD-1 blockade highlight potential analysis dynamically assess systemic burden during ICI open therapeutic window future intervention. ClinicalTrials.gov registration: NCT03044613 .
Язык: Английский
Процитировано
44
Cancers, Год журнала: 2024, Номер 16(5), С. 940 - 940
Опубликована: Фев. 26, 2024
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 where it aids identifying genomic markers and resistance mechanisms. This review explores the evolving landscape of utilizing liquid biopsies, specifically circulating (ctDNA), management NSCLC with
Язык: Английский
Процитировано
16
IntechOpen eBooks, Год журнала: 2025, Номер unknown
Опубликована: Фев. 27, 2025
Metastatic cancer remains a major challenge in oncology, often diagnosed late with limited intervention options. This chapter highlights the role of circulating tumor cells (CTCs) and DNA (ctDNA) as biomarkers for early detection, diagnosis, prognosis. Liquid biopsy, non-invasive method, analyzes blood components like CTCs, which provide insights into heterogeneity metastatic potential, ctDNA, reflects genetic mutations burden. These enable real-time monitoring, aiding understanding progression, treatment response, residual disease, resistance mechanisms. Advances detection methods emphasize their clinical relevance personalized treatment. Integrating CTCs ctDNA oncology could revolutionize management through individualized strategies, enhancing outcomes. The concludes challenges future directions implementing these precision oncology.
Язык: Английский
Процитировано
2
Science, Год журнала: 2024, Номер 383(6680), С. 260 - 261
Опубликована: Янв. 18, 2024
Attenuation of cell-free DNA clearance in vivo is an alternative strategy to maximize recovery.
Язык: Английский
Процитировано
8
Current Oncology, Год журнала: 2024, Номер 31(1), С. 482 - 500
Опубликована: Янв. 13, 2024
DNA methylation is a fundamental mechanism of epigenetic control in cells and its dysregulation strongly implicated cancer development. Cancers possess an extensively hypomethylated genome with focal regions hypermethylation at CPG islands. Due to the highly conserved nature cancer-specific methylation, detection cell-free plasma using liquid biopsies constitutes area interest biomarker research. The advent next-generation sequencing newer computational technologies have allowed for development diagnostic prognostic biomarkers that utilize profiling diagnose disease stratify risk. Methylome-based predictive can determine response anti-cancer therapy. An additional emerging application these minimal residual monitoring. Several key challenges need be addressed before cfDNA-based become fully integrated into practice. first relates biology stability cfDNA. second concerns clinical validity generalizability methylation-based assays, many which are type-specific. third involves their practicability, stumbling block translating from bench clinic. Future work on developing pan-cancer assays respective validities confirmed well-designed, prospective trials crucial pushing greater use tools oncology.
Язык: Английский
Процитировано
7
Cancer Discovery, Год журнала: 2024, Номер 14(6), С. 915 - 919
Опубликована: Июнь 3, 2024
Summary: Drug-tolerant residual disease (DTRD) after the initial maximal response to a systemic therapy can serve as tumor reservoir for development of acquired drug resistance and represents major clinical challenge across various cancers types therapies. To unlock next frontier in precision oncology, we propose fundamental paradigm shift treatment metastatic with sharpened focus towards defining, monitoring, therapeutically targeting DTRD state.
Язык: Английский
Процитировано
7
Clinical Cancer Research, Год журнала: 2024, Номер 30(22), С. 5034 - 5041
Опубликована: Сен. 13, 2024
Abstract Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The RECIST guidelines based on repeat imaging widely adopted in clinical trials, used identify active regimens that may change practice, contribute regulatory approvals. However, these criteria do not provide insight before 6 12 weeks treatment typically require patients have measurable disease. Recent data suggest measuring on-treatment changes the amount or proportion ctDNA peripheral blood plasma accurately responding nonresponding cancers at earlier time points. Over past year, working group has evaluated current evidence kinetics as a biomarker early endpoint trials areas focus future research validation. Here, we outline requirement large standardized trial datasets, greater scrutiny optimal collection points assay thresholds, consideration body patient opinions. In particular, clinically meaningful abundance likely differ by type class must be assessed can considered potential pan-cancer evaluation biomarker. Despite need additional data, minimally invasive measurements hold promise build upon existing assessments such offer opportunities developing novel endpoints modern trials.
Язык: Английский
Процитировано
7
Molecular Biomedicine, Год журнала: 2025, Номер 6(1)
Опубликована: Март 20, 2025
Abstract Cancer ranks among the most lethal diseases worldwide. Tissue biopsy is currently primary method for diagnosis and biological analysis of various solid tumors. However, this has some disadvantages related to insufficient tissue specimen collection intratumoral heterogeneity. Liquid a noninvasive approach identifying cancer-related biomarkers in peripheral blood, which allows repetitive sampling across multiple time points. In field liquid biopsy, representative include circulating tumor cells (CTCs), DNA (ctDNA), exosomes. Many studies have evaluated prognostic predictive roles CTCs ctDNA Although these limitations, results appear consistently demonstrate correlations high CTC counts mutations with lower survival rates cancer patients. Similarly, reduction throughout therapy may be potential indicator treatment response advanced Moreover, biochemical characteristics can provide information about biology as well resistance mechanisms against targeted therapy. This review discusses current clinical applications patients, emphasizing its possible utility outcome prediction decision-making.
Язык: Английский
Процитировано
1
Cancers, Год журнала: 2024, Номер 16(6), С. 1197 - 1197
Опубликована: Март 18, 2024
Cutaneous melanoma, an aggressive malignancy, has undergone significant transformation in clinical management with the introduction of immune checkpoint inhibitors (ICIs) and targeted therapies. Current monitoring methods, such as imaging scans, present limitations, prompting exploration alternative biomarkers. This review comprehensively explores role circulating tumor DNA (ctDNA) advanced covering technical aspects, detection its prognostic predictive value. Recent findings underscore ctDNA’s potential applications implications practice. emphasizes need for precise dynamic biomarkers melanoma care, positioning ctDNA a promising blood-based tool prognosis, treatment response, resistance mechanisms. The nuances detection, association mutations, guiding therapeutic decisions immunotherapy therapy multifaceted utility, marking paradigm shift decision-making offering trajectory personalized informed care melanoma.
Язык: Английский
Процитировано
6
Scientific Reports, Год журнала: 2024, Номер 14(1)
Опубликована: Июнь 18, 2024
Programmed Death Receptor 1 (PD-1) inhibitors, when combined with chemotherapy, have exhibited notable effectiveness in enhancing the survival outcomes of patients afflicted advanced gastric cancer. However, it is important to acknowledge that not all derive substantial benefits from this therapeutic approach, highlighting crucial necessity identifying efficacious biomarkers inform immunotherapy interventions. In study, we sought investigate predictive utility circulating tumor DNA (ctDNA) as a biomarker cohort 30 diagnosed cancer, whom underwent first-line treatment involving PD-1 inhibitor administration alongside chemotherapy. We procured peripheral blood samples both at baseline and following completion two cycles. Additionally, tissue specimens were collected for purpose genomic alteration assessment, employing 47-gene 737-gene next-generation sequencing panels plasma tissue, respectively. delineated ctDNA response eradication maximum variant allele frequencies relative levels. Notably, objective rate among individuals exhibiting proved significantly superior comparison non-responders (P = 0.0073). Furthermore, who manifested experienced markedly prolonged progression-free (PFS) overall (OS) juxtaposed those devoid (median PFS: 15.6 vs. 6.0 months, P 0.003; median OS: reached [NR] 9.0 0.011). summation, cancer receiving inhibitors dynamic changes can serve potential predicting efficacy long-term outcomes.
Язык: Английский
Процитировано
6