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1.
JAMA Netw Open ; 7(5): e2410171, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38713467

RESUMO

This cross-sectional study evaluates the information on a circulating tumor DNA test available to the public on popular internet resources.


Assuntos
Acesso à Informação , Humanos , Biópsia Líquida/métodos , Feminino , Masculino , Pessoa de Meia-Idade
2.
Sci Rep ; 14(1): 10199, 2024 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702437

RESUMO

In pancreatic ductal adenocarcinoma (PDAC) patients, the importance of peritoneal lavage cytology, which indicates unresectability, remains controversial. This study sought to determine whether positive peritoneal lavage cytology (CY+) precludes pancreatectomy. Furthermore, we propose a novel liquid biopsy using peritoneal lavage fluid to detect viable peritoneal tumor cells (v-PTCs) with TelomeScan F35, a telomerase-specific replication-selective adenovirus engineered to express green fluorescent protein. Resectable cytologically or histologically proven PDAC patients (n = 53) were enrolled. CY was conducted immediately following laparotomy. The resulting fluid was examined by conventional cytology (conv-CY; Papanicolaou staining and MOC-31 immunostaining) and by the novel technique (Telo-CY; using TelomeScan F35). Of them, 5 and 12 were conv-CY+ and Telo-CY+, respectively. All underwent pancreatectomy. The two double-CY+ (conv-CY+ and Telo-CY+) patients showed early peritoneal recurrence (P-rec) postoperatively, despite adjuvant chemotherapy. None of the three conv-CY+ Telo-CY- patients exhibited P-rec. Six of the 10 Telo-CY+ conv-CY- patients (60%) relapsed with P-rec. Of the remaining 38 double-CY- [conv-CY-, Telo-CY-, conv-CY± (Class III)] patients, 3 (8.3%) exhibited P-rec. Although conv-CY+ status predicted poor prognosis and a higher risk of P-rec, Telo-CY was more sensitive for detecting v-PTC. Staging laparoscopy and performing conv-CY and Telo-CY are needed to confirm the indication for pancreatectomy.


Assuntos
Carcinoma Ductal Pancreático , Pancreatectomia , Neoplasias Pancreáticas , Lavagem Peritoneal , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/diagnóstico , Citodiagnóstico/métodos , Idoso de 80 Anos ou mais , Recidiva Local de Neoplasia/patologia , Biópsia Líquida/métodos , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/diagnóstico , Adulto , Citologia
3.
J Transl Med ; 22(1): 462, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750555

RESUMO

BACKGROUND: Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. METHODS: Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. RESULTS: The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. CONCLUSIONS: Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.


Assuntos
Genômica , Mutação em Linhagem Germinativa , Neoplasias , Humanos , Feminino , Biópsia Líquida , Neoplasias/genética , Neoplasias/patologia , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Mutação em Linhagem Germinativa/genética , Genômica/métodos , Adulto , Idoso , Células Germinativas/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Predisposição Genética para Doença
4.
PLoS One ; 19(5): e0302129, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753705

RESUMO

Emerging technologies focused on the detection and quantification of circulating tumor DNA (ctDNA) in blood show extensive potential for managing patient treatment decisions, informing risk of recurrence, and predicting response to therapy. Currently available tissue-informed approaches are often limited by the need for additional sequencing of normal tissue or peripheral mononuclear cells to identify non-tumor-derived alterations while tissue-naïve approaches are often limited in sensitivity. Here we present the analytical validation for a novel ctDNA monitoring assay, FoundationOne®Tracker. The assay utilizes somatic alterations from comprehensive genomic profiling (CGP) of tumor tissue. A novel algorithm identifies monitorable alterations with a high probability of being somatic and computationally filters non-tumor-derived alterations such as germline or clonal hematopoiesis variants without the need for sequencing of additional samples. Monitorable alterations identified from tissue CGP are then quantified in blood using a multiplex polymerase chain reaction assay based on the validated SignateraTM assay. The analytical specificity of the plasma workflow is shown to be 99.6% at the sample level. Analytical sensitivity is shown to be >97.3% at ≥5 mean tumor molecules per mL of plasma (MTM/mL) when tested with the most conservative configuration using only two monitorable alterations. The assay also demonstrates high analytical accuracy when compared to liquid biopsy-based CGP as well as high qualitative (measured 100% PPA) and quantitative precision (<11.2% coefficient of variation).


Assuntos
DNA Tumoral Circulante , Neoplasias , Humanos , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Neoplasias/genética , Neoplasias/sangue , Neoplasias/diagnóstico , Genômica/métodos , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Sensibilidade e Especificidade , Algoritmos , Reação em Cadeia da Polimerase Multiplex/métodos , Biópsia Líquida/métodos
5.
Anal Chim Acta ; 1308: 342578, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38740462

RESUMO

Cancer is one of the serious threats to public life and health. Early diagnosis, real-time monitoring, and individualized treatment are the keys to improve the survival rate and prolong the survival time of cancer patients. Liquid biopsy is a potential technique for cancer early diagnosis due to its non-invasive and continuous monitoring properties. However, most current liquid biopsy techniques lack the ability to detect cancers at the early stage. Therefore, effective detection of a variety of cancers is expected through the combination of various techniques. Recently, DNA frameworks with tailorable functionality and precise addressability have attracted wide spread attention in biomedical applications, especially in detecting cancer biomarkers such as circulating tumor cells (CTCs), exosomes and circulating tumor nucleic acid (ctNA). Encouragingly, DNA frameworks perform outstanding in detecting these cancer markers, but also face some challenges and opportunities. In this review, we first briefly introduced the development of DNA frameworks and its typical structural characteristics and advantages. Then, we mainly focus on the recent progress of DNA frameworks in detecting commonly used cancer markers in liquid-biopsy. We summarize the advantages and applications of DNA frameworks for detecting CTCs, exosomes and ctNA. Furthermore, we provide an outlook on the possible opportunities and challenges for exploiting the structural advantages of DNA frameworks in the field of cancer diagnosis. Finally, we envision the marriage of DNA frameworks with other emerging materials and technologies to develop the next generation of disease diagnostic biosensors.


Assuntos
DNA , Neoplasias , Biópsia Líquida/métodos , Humanos , DNA/química , Neoplasias/diagnóstico , Neoplasias/patologia , Biomarcadores Tumorais/análise , Células Neoplásicas Circulantes/patologia , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/análise , Exossomos/química
6.
Zhonghua Yi Xue Za Zhi ; 104(18): 1547-1554, 2024 May 14.
Artigo em Chinês | MEDLINE | ID: mdl-38742339

RESUMO

Lung cancer remains the most prevalent and lethal malignancy in our country. Early diagnosis and treatment are crucial for improving patient prognosis in lung cancer/pulmonary nodules. Recent advancements in non-invasive/minimally invasive liquid biopsy, multi-omics, and artificial intelligence technologies have significantly enhanced the accuracy of early lung cancer/pulmonary nodule diagnosis. However, an early diagnostic method with both high sensitivity and specificity is yet to be established. Furthermore, addressing the methods and extent of early precision surgery, local precision therapy, perioperative combined treatment, and postoperative recurrence and metastasis monitoring are urgent challenges in the early management of lung cancer/pulmonary nodules. Integrating the advantages of various treatment strategies and formulating personalized and precise treatment plans is key to further improving patient survival. In the future, while exploring new therapeutic strategies, it is necessary to continuously search for biomarkers to identify the population that will benefit from the treatment effectively. Additionally, large-sample randomized controlled clinical studies should be conducted to investigate the benefits of long-term patient survival under a diverse range of treatment strategies.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Prognóstico , Biópsia Líquida , Sensibilidade e Especificidade
7.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732099

RESUMO

Medulloblastoma is the most common malignant brain tumor in childhood. Initial treatment generally includes surgery, irradiation, and chemotherapy. Approximately 20-30% of patients will experience a recurrence, which portends a very poor prognosis. The current standard of care for evaluation for relapse includes radiographic surveillance with magnetic resonance imaging at regular intervals. The presence of circulating tumor DNA in the cerebrospinal fluid has been demonstrated to be a predictor of a higher risk of progression in a research setting for patients with medulloblastoma treated on a prospective single institution clinical trial. We have previously published and clinically validated a liquid-biopsy-based genetic assay utilizing low-pass whole genome sequencing to detect copy number alterations in circulating tumor DNA. Here, we present two teenage patients with posterior fossa medulloblastoma with recurrent disease who have been monitored with serial liquid biopsies showing tumor evolution over time, demonstrating the clinical utility of these approaches.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Recidiva Local de Neoplasia , Humanos , Meduloblastoma/líquido cefalorraquidiano , Meduloblastoma/genética , Meduloblastoma/diagnóstico , Meduloblastoma/patologia , Meduloblastoma/diagnóstico por imagem , Biópsia Líquida/métodos , Recidiva Local de Neoplasia/líquido cefalorraquidiano , Recidiva Local de Neoplasia/genética , Adolescente , Neoplasias Cerebelares/líquido cefalorraquidiano , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/genética , Masculino , DNA Tumoral Circulante/líquido cefalorraquidiano , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Feminino , Progressão da Doença , Imageamento por Ressonância Magnética
8.
Cancer Control ; 31: 10732748241255548, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38764160

RESUMO

Background: Ovarian cancer stands as the deadliest malignant tumor within the female reproductive tract. As a result of the absence of effective diagnostic and monitoring markers, 75% of ovarian cancer cases are diagnosed at a late stage, leading to a mere 50% survival rate within five years. The advancement of molecular biology is essential for accurate diagnosis and treatment of ovarian cancer. Methods: A review of several randomized clinical trials, focusing on the ovarian cancer, was undertaken. The advancement of molecular biology and diagnostic methods related to accurate diagnosis and treatment of ovarian cancer were examined. Results: Liquid biopsy is an innovative method of detecting malignant tumors that has gained increasing attention over the past few years. Cell-free DNA assay-based liquid biopsies show potential in delineating tumor status heterogeneity and tracking tumor recurrence. DNA methylation influences a multitude of biological functions and diseases, especially during the initial phases of cancer. The cell-free DNA methylation profiling system has emerged as a sensitive and non-invasive technique for identifying and detecting the biological origins of cancer. It holds promise as a biomarker, enabling early screening, recurrence monitoring, and prognostic evaluation of cancer. Conclusions: This review evaluates recent advancements and challenges associated with cell-free DNA methylation analysis for the diagnosis, prognosis monitoring, and assessment of therapeutic responses in the management of ovarian cancers, aiming to offer guidance for precise diagnosis and treatment of this disease.


Ovarian cancer stands as the deadliest malignant tumor within the female reproductive tract. As a result of the absence of effective diagnostic and monitoring markers, 75% of ovarian cancer cases are diagnosed at a late stage, leading to a mere 50% survival rate within five years. Nearly 80% of advanced stages have a poor prognosis or recurrence within five years. Ovarian cancer is linked to a grim long-term prognosis attributable to its elevated mortality and recurrence rates. The advancement of molecular biology and diagnostic methods is essential for accurate diagnosis and treatment of ovarian cancer. Liquid biopsy is an innovative method of detecting malignant tumors that has gained increasing attention over the past few years. Cell-free DNA assay-based liquid biopsies show potential in delineating tumor status heterogeneity and tracking tumor recurrence. DNA methylation represents a prevalent epigenetic modification. DNA methylation influences a multitude of biological functions and diseases, especially during the initial phases of cancer. The cell-free DNA methylation profiling system has emerged as a sensitive and non-invasive technique for identifying and detecting the biological origins of cancer. This review assesses recent progress and obstacles linked to cell-free DNA methylation analysis for diagnosing, prognostic monitoring, and evaluating therapeutic responses in managing ovarian cancers.


Assuntos
Biomarcadores Tumorais , Metilação de DNA , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Prognóstico , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , Biópsia Líquida/métodos
9.
Technol Cancer Res Treat ; 23: 15330338241252706, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766867

RESUMO

Objectives: In this study, stool samples were evaluated for tumor mutation analysis via a targeted next generation sequencing (NGS) approach in a small patient cohort suffering from localized rectal cancer. Introduction: Colorectal cancer (CRC) causes the second highest cancer-related death rate worldwide. Thus, improvements in disease assessment and monitoring that may facilitate treatment allocation and allow organ-sparing "watch-and-wait" treatment strategies are highly relevant for a significant number of CRC patients. Methods: Stool-based results were compared with mutation profiles derived from liquid biopsies and the gold standard procedure of tumor biopsy from the same patients. A workflow was established that enables the detection of de-novo tumor mutations in stool samples of CRC patients via ultra-sensitive cell-free tumor DNA target enrichment. Results: Notably, only a 19% overall concordance was found in mutational profiles across the compared sample specimens of stool, tumor, and liquid biopsies. Conclusion: Based on these results, the analysis of stool and liquid biopsy samples can provide important additional information on tumor heterogeneity and potentially on the assessment of minimal residual disease and clonal tumor evolution.


Assuntos
Biomarcadores Tumorais , Fezes , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Neoplasias Retais , Humanos , Fezes/química , Neoplasias Retais/genética , Neoplasias Retais/patologia , Neoplasias Retais/sangue , Biomarcadores Tumorais/genética , Biópsia Líquida/métodos , Feminino , Masculino , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Pessoa de Meia-Idade , Idoso , Análise Mutacional de DNA , Heterogeneidade Genética , DNA de Neoplasias/sangue , DNA de Neoplasias/genética
10.
Hepatol Commun ; 8(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38727682

RESUMO

BACKGROUND: Hepatoblastoma and HCC are the most common malignant hepatocellular tumors seen in children. The aim of this study was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide real-time information about tumor response to therapy. METHODS: For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye used clinically to identify malignant liver cells during surgery. We assessed ICG accumulation in cell lines using fluorescence microscopy and flow cytometry. For our CTC test, we developed a panel of liver tumor-specific markers, including ICG, Glypican-3, and DAPI, and tested it with cell lines and noncancer control blood samples. We then used this panel to analyze whole-blood samples for CTC burden with a cohort of 15 patients with hepatoblastoma and HCC and correlated with patient characteristics and outcomes. RESULTS: We showed that ICG accumulation is specific to liver cancer cells, compared to nonmalignant liver cells, non-liver solid tumor cells, and other nonmalignant cells, and can be used to identify liver tumor cells in a mixed population of cells. Experiments with the ICG/Glypican-3/DAPI panel showed that it specifically tagged malignant liver cells. Using patient samples, we found that CTC burden from sequential blood samples from the same patients mirrored the patients' responses to therapy. CONCLUSIONS: Our novel ICG-based liquid biopsy test for CTCs can be used to specifically detect and quantify CTCs in the blood of pediatric patients with liver cancer.


Assuntos
Carcinoma Hepatocelular , Hepatoblastoma , Verde de Indocianina , Neoplasias Hepáticas , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Biópsia Líquida , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Criança , Feminino , Masculino , Pré-Escolar , Hepatoblastoma/sangue , Hepatoblastoma/patologia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Biomarcadores Tumorais/sangue , Lactente , Adolescente , Corantes
11.
ACS Nano ; 18(20): 12781-12794, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38733343

RESUMO

Circulating tumor DNA (ctDNA) detection has been acknowledged as a promising liquid biopsy approach for cancer diagnosis, with various ctDNA assays used for early detection and treatment monitoring. Dispersible magnetic nanoparticle-based electrochemical detection methods have been proposed as promising candidates for ctDNA detection based on the detection performance and features of the platform material. This study proposes a nanoparticle surface-localized genetic amplification approach by integrating Fe3O4-Au core-shell nanoparticles into polymerase chain reactions (PCR). These highly dispersible and magnetically responsive superparamagnetic nanoparticles act as nano-electrodes that amplify and accumulate target ctDNA in situ on the nanoparticle surface upon PCR amplification. These nanoparticles are subsequently captured and subjected to repetitive electrochemical measurements to induce reconfiguration-mediated signal amplification for ultrasensitive (∼3 aM) and rapid (∼7 min) metastatic breast cancer ctDNA detection in vitro. The detection platform can also detect metastatic biomarkers from in vivo samples, highlighting the potential for clinical applications and further expansion to rapid and ultrasensitive multiplex detection of various cancers.


Assuntos
DNA Tumoral Circulante , Eletrodos , Humanos , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Biópsia Líquida , Amplificação de Genes , Nanopartículas de Magnetita/química , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Ouro/química , Propriedades de Superfície , Técnicas Eletroquímicas/métodos , Reação em Cadeia da Polimerase , Feminino
12.
Int J Mol Sci ; 25(10)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38791138

RESUMO

An early diagnosis of cancer is fundamental not only in regard to reducing its mortality rate but also in terms of counteracting the progression of the tumor in the initial stages. Breast cancer (BC) is the most common tumor pathology in women and the second deathliest cancer worldwide, although its survival rate is increasing thanks to improvements in screening programs. However, the most common techniques to detect a breast tumor tend to be time-consuming, unspecific or invasive. Herein, the use of untargeted hydrophilic interaction liquid chromatography-mass spectrometry analysis appears as an analytical technique with potential use for the early detection of biomarkers in liquid biopsies from BC patients. In this research, plasma samples from 134 BC patients were compared with 136 from healthy controls (HC), and multivariate statistical analyses showed a clear separation between four BC phenotypes (LA, LB, HER2, and TN) and the HC group. As a result, we identified two candidate biomarkers that discriminated between the groups under study with a VIP > 1 and an AUC of 0.958. Thus, targeting the specific aberrant metabolic pathways in future studies may allow for better molecular stratification or early detection of the disease.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Interações Hidrofóbicas e Hidrofílicas , Metabolômica , Humanos , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Biomarcadores Tumorais/sangue , Biópsia Líquida/métodos , Metabolômica/métodos , Pessoa de Meia-Idade , Cromatografia Líquida/métodos , Idoso , Adulto , Espectrometria de Massas/métodos , Espectrometria de Massa com Cromatografia Líquida
13.
Int J Mol Sci ; 25(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38791247

RESUMO

Over the last decades, the survival of multiple myeloma (MM) patients has considerably improved. However, despite the availability of new treatments, most patients still relapse and become therapy-resistant at some point in the disease evolution. The mutation profile has an impact on MM patients' outcome, while typically evolving over time. Because of the patchy bone marrow (BM) infiltration pattern, the analysis of a single bone marrow sample can lead to an underestimation of the known genetic heterogeneity in MM. As a result, interest is shifting towards blood-derived liquid biopsies, which allow for a more comprehensive and non-invasive genetic interrogation without the discomfort of repeated BM aspirations. In this review, we compare the application potential for mutation profiling in MM of circulating-tumor-cell-derived DNA, cell-free DNA and extracellular-vesicle-derived DNA, while also addressing the challenges associated with their use.


Assuntos
Mieloma Múltiplo , Mutação , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Mieloma Múltiplo/diagnóstico , Humanos , Biópsia Líquida/métodos , DNA Tumoral Circulante/genética , Ácidos Nucleicos Livres/genética , Biomarcadores Tumorais/genética , Análise Mutacional de DNA/métodos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo
14.
Mol Biomed ; 5(1): 17, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38724687

RESUMO

Uveal cancer (UM) offers a complex molecular landscape characterized by substantial heterogeneity, both on the genetic and epigenetic levels. This heterogeneity plays a critical position in shaping the behavior and response to therapy for this uncommon ocular malignancy. Targeted treatments with gene-specific therapeutic molecules may prove useful in overcoming radiation resistance, however, the diverse molecular makeups of UM call for a patient-specific approach in therapy procedures. We need to understand the intricate molecular landscape of UM to develop targeted treatments customized to each patient's specific genetic mutations. One of the promising approaches is using liquid biopsies, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), for detecting and monitoring the disease at the early stages. These non-invasive methods can help us identify the most effective treatment strategies for each patient. Single-cellular is a brand-new analysis platform that gives treasured insights into diagnosis, prognosis, and remedy. The incorporation of this data with known clinical and genomics information will give a better understanding of the complicated molecular mechanisms that UM diseases exploit. In this review, we focused on the heterogeneity and molecular panorama of UM, and to achieve this goal, the authors conducted an exhaustive literature evaluation spanning 1998 to 2023, using keywords like "uveal melanoma, "heterogeneity". "Targeted therapies"," "CTCs," and "single-cellular analysis".


Assuntos
Heterogeneidade Genética , Melanoma , Terapia de Alvo Molecular , Neoplasias Uveais , Humanos , Melanoma/genética , Melanoma/patologia , Melanoma/terapia , Melanoma/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Neoplasias Uveais/genética , Neoplasias Uveais/terapia , Neoplasias Uveais/patologia , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Biomarcadores Tumorais/genética , Mutação , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Biópsia Líquida/métodos
15.
Sci Rep ; 14(1): 11398, 2024 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762534

RESUMO

Glioblastoma (GB) is a devastating tumor of the central nervous system characterized by a poor prognosis. One of the best-established predictive biomarker in IDH-wildtype GB is O6-methylguanine-DNA methyltransferase (MGMT) methylation (mMGMT), which is associated with improved treatment response and survival. However, current efforts to monitor GB patients through mMGMT detection have proven unsuccessful. Small extracellular vesicles (sEVs) hold potential as a key element that could revolutionize clinical practice by offering new possibilities for liquid biopsy. This study aimed to determine the utility of sEV-based liquid biopsy as a predictive biomarker and disease monitoring tool in patients with IDH-wildtype GB. Our findings show consistent results with tissue-based analysis, achieving a remarkable sensitivity of 85.7% for detecting mMGMT in liquid biopsy, the highest reported to date. Moreover, we suggested that liquid biopsy assessment of sEV-DNA could be a powerful tool for monitoring disease progression in IDH-wildtype GB patients. This study highlights the critical significance of overcoming molecular underdetection, which can lead to missed treatment opportunities and misdiagnoses, possibly resulting in ineffective therapies. The outcomes of our research significantly contribute to the field of sEV-DNA-based liquid biopsy, providing valuable insights into tumor tissue heterogeneity and establishing it as a promising tool for detecting GB biomarkers. These results have substantial implications for advancing predictive and therapeutic approaches in the context of GB and warrant further exploration and validation in clinical settings.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas , Metilação de DNA , Metilases de Modificação do DNA , Enzimas Reparadoras do DNA , Vesículas Extracelulares , Glioblastoma , Proteínas Supressoras de Tumor , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/diagnóstico , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Biópsia Líquida/métodos , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Masculino , Feminino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/diagnóstico , Idoso , Adulto , Prognóstico
16.
Mol Cancer ; 23(1): 76, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622694

RESUMO

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a new type of non-coding RNAs (ncRNAs) produced by the specific cleavage of precursor or mature tRNAs. tsRNAs are involved in various basic biological processes such as epigenetic, transcriptional, post-transcriptional, and translation regulation, thereby affecting the occurrence and development of various human diseases, including cancers. Recent studies have shown that tsRNAs play an important role in tumorigenesis by regulating biological behaviors such as malignant proliferation, invasion and metastasis, angiogenesis, immune response, tumor resistance, and tumor metabolism reprogramming. These may be new potential targets for tumor treatment. Furthermore, tsRNAs can exist abundantly and stably in various bodily fluids (e.g., blood, serum, and urine) in the form of free or encapsulated extracellular vesicles, thereby affecting intercellular communication in the tumor microenvironment (TME). Meanwhile, their abnormal expression is closely related to the clinicopathological features of tumor patients, such as tumor staging, lymph node metastasis, and poor prognosis of tumor patients; thus, tsRNAs can be served as a novel type of liquid biopsy biomarker. This review summarizes the discovery, production, and expression of tsRNAs and analyzes their molecular mechanisms in tumor development and potential applications in tumor therapy, which may provide new strategies for early diagnosis and targeted therapy of tumors.


Assuntos
Neoplasias , RNA de Transferência , Humanos , RNA de Transferência/genética , RNA de Transferência/metabolismo , Neoplasias/genética , Carcinogênese , Biópsia Líquida , Microambiente Tumoral/genética
17.
Int J Mol Sci ; 25(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674117

RESUMO

Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of response to combined ICI and SABR (I-SABR) in liquid biopsy from oligoprogressive patients in a prospective observational multicenter study. Cohort A includes metastatic patients in oligoprogression to ICI maintaining the same ICI due to clinical benefit and who receive concomitant SABR. B is a comparative group of oligometastatic patients receiving only SABR. Blood samples are extracted at baseline (T1), after the first (T2) and last (T3) fraction, two months post-SABR (T4) and at further progression (TP). Response is evaluated by iRECIST and defined by the objective response rate (ORR)-complete and partial responses. We assess peripheral blood mononuclear cells (PBMCs), circulating cell-free DNA (cfDNA) and small RNA from extracellular vesicles. Twenty-seven patients could be analyzed (cohort A: n = 19; B: n = 8). Most were males with non-small cell lung cancer and one progressing lesion. With a median follow-up of 6 months, the last ORR was 63% (26% complete and 37% partial response). A decrease in cfDNA from T2 to T3 correlated with a good response. At T2, CD8+PD1+ and CD8+PDL1+ cells were increased in non-responders and responders, respectively. At T2, 27 microRNAs were differentially expressed. These are potential biomarkers of response to I-SABR in oligoprogressive disease.


Assuntos
Biomarcadores Tumorais , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Radiocirurgia , Humanos , Masculino , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Feminino , Idoso , Biomarcadores Tumorais/sangue , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Ácidos Nucleicos Livres/sangue , Estudos Prospectivos , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Idoso de 80 Anos ou mais , Metástase Neoplásica , Progressão da Doença , Biópsia Líquida/métodos , Leucócitos Mononucleares/metabolismo , Resultado do Tratamento
18.
World J Gastroenterol ; 30(15): 2175-2178, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38681986

RESUMO

With the rapid development of science and technology, cell-free DNA (cfDNA) is rapidly becoming an important biomarker for tumor diagnosis, monitoring and prognosis, and this cfDNA-based liquid biopsy technology has great potential to become an important part of precision medicine. cfDNA is the total amount of free DNA in the systemic circulation, including DNA fragments derived from tumor cells and all other somatic cells. Tumor cells release fragments of DNA into the bloodstream, and this source of cfDNA is called circulating tumor DNA (ctDNA). cfDNA detection has become a major focus in the field of tumor research in recent years, which provides a new opportunity for non-invasive diagnosis and prognosis of cancer. In this paper, we discuss the limitations of the study on the origin and dynamics analysis of ctDNA, and how to solve these problems in the future. Although the future faces major challenges, it also contains great potential.


Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , Neoplasias , Humanos , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/sangue , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Biópsia Líquida/métodos , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patologia , Medicina de Precisão/métodos , Prognóstico
19.
Biomolecules ; 14(4)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38672414

RESUMO

Small-cell lung cancer (SCLC) cases represent approximately 15% of all lung cancer cases, remaining a recalcitrant malignancy with poor survival and few treatment options. In the last few years, the addition of immunotherapy to chemotherapy improved clinical outcomes compared to chemotherapy alone, resulting in the current standard of care for SCLC. However, the advantage of immunotherapy only applies to a few SCLC patients, and predictive biomarkers selection are lacking for SCLC. In particular, due to some features of SCLC, such as high heterogeneity, elevated cell plasticity, and low-quality tissue samples, SCLC biopsies cannot be used as biomarkers. Therefore, the characterization of the tumor and, subsequently, the selection of an appropriate therapeutic combination may benefit greatly from liquid biopsy. Soluble factors, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs) are now useful tools in the characterization of SCLC. This review summarizes the most recent data on biomarkers detectable with liquid biopsy, emphasizing their role in supporting tumor detection and their potential role in SCLC treatment choice.


Assuntos
Biomarcadores Tumorais , Imunoterapia , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Carcinoma de Pequenas Células do Pulmão , Humanos , Biópsia Líquida/métodos , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/diagnóstico , Imunoterapia/métodos , Biomarcadores Tumorais/metabolismo , Células Neoplásicas Circulantes/patologia , Células Neoplásicas Circulantes/metabolismo , DNA Tumoral Circulante/sangue , Vesículas Extracelulares/metabolismo
20.
Int J Mol Sci ; 25(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38673779

RESUMO

Meningiomas are tumors of the central nervous system that vary in their presentation, ranging from benign and slow-growing to highly aggressive. The standard method for diagnosing and classifying meningiomas involves invasive surgery and can fail to provide accurate prognostic information. Liquid biopsy methods, which exploit circulating tumor biomarkers such as DNA, extracellular vesicles, micro-RNA, proteins, and more, offer a non-invasive and dynamic approach for tumor classification, prognostication, and evaluating treatment response. Currently, a clinically approved liquid biopsy test for meningiomas does not exist. This review provides a discussion of current research and the challenges of implementing liquid biopsy techniques for advancing meningioma patient care.


Assuntos
Biomarcadores Tumorais , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico , Meningioma/patologia , Biópsia Líquida/métodos , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/patologia , Vesículas Extracelulares/metabolismo , Prognóstico
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