scholarly journals EV Translational Horizons as Viewed Across the Complex Landscape of Liquid Biopsies

2021 ◽  
Vol 9 ◽  
Author(s):  
Bryce Killingsworth ◽  
Joshua A. Welsh ◽  
Jennifer C. Jones
Keyword(s):  
Extracellular Vesicle ◽  
Current Evidence ◽  
Liquid Biopsies ◽  
Ribonucleoprotein Complexes ◽  
Biological Studies ◽  
Complex Landscape ◽  
Clinical Correlations ◽  
Treatment Responses ◽  
Therapeutic Tools ◽  
Monitoring Treatment

Extracellular Vesicle (EV)-based diagnostic and therapeutic tools are an area of intensive study and substantial promise, but EVs as liquid biopsies have advanced years ahead of EVs as therapeutic tools. EVs are emerging as a promising approach for detecting tumors, evaluating the molecular profiles of known disease, and monitoring treatment responses. Although correlative assays based on liquid biopsies are already having an impact on translational studies and clinical practice, much remains to be learned before these assays will be optimized for clinical correlations, functional biological studies, and therapeutic use. What follows is an overview of current evidence supporting the investigation and use of liquid biopsies, organized by specific liquid biopsy components available for analysis, along with a summary of what challenges must be overcome before these assays will provide functional biological insights into the pathogenesis and treatment of disease. The same challenges must also be overcome before it will be feasible to measure and monitor the dosing, distribution, pharmacokinetics, and delivery of EV therapeutics and their cargo in complex biofluids where EVs and circulate with and are co-isolated with a number of other nanoscale materials, including lipoproteins (LPPs), ribonucleoprotein complexes (RNPs), and cell free nucleic acids (cfNA).

scholarly journals Tracking extracellular vesicle phenotypic changes enables treatment monitoring in melanoma

2020 ◽  
Vol 6 (9) ◽  
pp. eaax3223 ◽  
Author(s):  
Jing Wang ◽  
Alain Wuethrich ◽  
Abu Ali Ibn Sina ◽  
Rebecca E. Lane ◽  
Lynlee L. Lin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Targeted Therapy ◽  
Extracellular Vesicle ◽  
Patient Treatment ◽  
Preclinical Model ◽  
Phenotypic Evolution ◽  
Therapeutic Outcomes ◽  
Surface Enhanced Raman ◽  
Treatment Responses ◽  
Monitoring Treatment

Monitoring targeted therapy in real time for cancer patients could provide vital information about the development of drug resistance and improve therapeutic outcomes. Extracellular vesicles (EVs) have recently emerged as a promising cancer biomarker, and EV phenotyping shows high potential for monitoring treatment responses. Here, we demonstrate the feasibility of monitoring patient treatment responses based on the plasma EV phenotypic evolution using a multiplex EV phenotype analyzer chip (EPAC). EPAC incorporates the nanomixing-enhanced microchip and the multiplex surface-enhanced Raman scattering (SERS) nanotag system for direct EV phenotyping without EV enrichment. In a preclinical model, we observe the EV phenotypic heterogeneity and different phenotypic responses to the treatment. Furthermore, we successfully detect cancer-specific EV phenotypes from melanoma patient plasma. We longitudinally monitor the EV phenotypic evolution of eight melanoma patients receiving targeted therapy and find specific EV profiles involved in the development of drug resistance, reflecting the potential of EV phenotyping for monitoring treatment responses.

scholarly journals Towards Routine Implementation of Liquid Biopsies in Cancer Management: It Is Always Too Early, until Suddenly It Is Too Late

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 103
Author(s):  
Maarten J. IJzerman ◽  
Jasper de Boer ◽  
Arun Azad ◽  
Koen Degeling ◽  
Joel Geoghegan ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Clinical Laboratory ◽  
Genomic Analysis ◽  
Current Evidence ◽  
Liquid Biopsies ◽  
Blood Draw ◽  
Minimum Quality Standards ◽  
Cancer Management ◽  
Alternative Funding ◽  
And Performance

Blood-based liquid biopsies are considered a new and promising diagnostic and monitoring tool for cancer. As liquid biopsies only require a blood draw, they are non-invasive, potentially more rapid and assumed to be a less costly alternative to genomic analysis of tissue biopsies. A multi-disciplinary workshop (n = 98 registrations) was organized to discuss routine implementation of liquid biopsies in cancer management. Real-time polls were used to engage with experts’ about the current evidence of clinical utility and the barriers to implementation of liquid biopsies. Clinical, laboratory and health economics presentations were given to illustrate the opportunities and current levels of evidence, followed by three moderated break-out sessions to discuss applications. The workshop concluded that tumor-informed assays using next-generation sequencing (NGS) or PCR-based genotyping assays will most likely provide better clinical utility than tumor-agnostic assays, yet at a higher cost. For routine application, it will be essential to determine clinical utility, to define the minimum quality standards and performance of testing platforms and to ensure their use is integrated into current clinical workflows including how they complement tissue biopsies and imaging. Early health economic models may help identifying the most viable application of liquid biopsies. Alternative funding models for the translation of complex molecular diagnostics, such as liquid biopsies, may also be explored if clinical utility has been demonstrated and when their use is recommended in multi-disciplinary consensus guidelines.

Protein biomarkers in breast cancer-derived extracellular vesicles for use in liquid biopsies

2021 ◽  
Author(s):  
Dan Li ◽  
Wenjia Lai ◽  
Di Fan ◽  
Qiaojun Fang
Keyword(s):  
Breast Cancer ◽  
Early Diagnosis ◽  
Extracellular Vesicles ◽  
Liquid Biopsy ◽  
Breast Cancer Diagnosis ◽  
Extracellular Vesicle ◽  
Detection Methods ◽  
Protein Markers ◽  
Liquid Biopsies ◽  
Diagnosis And Prognosis

Breast cancer is the most common malignant disease in women worldwide. Early diagnosis and treatment can greatly improve the management of breast cancer. Liquid biopsies are becoming convenient detection methods for diagnosing and monitoring breast cancer due to their non-invasiveness and ability to provide real-time feedback. A range of liquid biopsy markers, including circulating tumor proteins, circulating tumor cells, and circulating tumor nucleic acids, have been implemented for breast cancer diagnosis and prognosis, with each having its own advantages and limitations. Circulating extracellular vesicles are messengers of intercellular communication that are packed with information from mother cells and are found in a wide variety of bodily fluids; thus, they are emerging as ideal candidates for liquid biopsy biomarkers. In this review, we summarize extracellular vesicle protein markers that can be potentially used for the early diagnosis and prognosis of breast cancer or determining its specific subtypes.

scholarly journals IFITM1 expression determines extracellular vesicle uptake in colorectal cancer

2021 ◽  
Author(s):  
Andrea Kelemen ◽  
Idan Carmi ◽  
Ádám Oszvald ◽  
Péter Lőrincz ◽  
Gábor Petővári ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transmembrane Protein ◽  
Extracellular Vesicle ◽  
Cellular Heterogeneity ◽  
Functional Difference ◽  
Proliferating Cells ◽  
Antiviral Responses ◽  
The Difference ◽  
Functional Relevance ◽  
Therapeutic Tools

AbstractThe majority of colorectal cancer (CRC) patients carry mutations in the APC gene, which lead to the unregulated activation of the Wnt pathway. Extracellular vesicles (EV) are considered potential therapeutic tools. Although CRC is a genetically heterogeneous disease, the significance of the intra-tumor heterogeneity in EV uptake of CRC cells is not yet known. By using mouse and patient-derived organoids, the currently available best model of capturing cellular heterogeneity, we found that Apc mutation induced the expression of interferon-induced transmembrane protein 1 (Ifitm1), a membrane protein that plays a major role in cellular antiviral responses. Importantly, organoids derived from IFITM1high CRC cells contained more proliferating cells and they had a markedly reduced uptake of fibroblast EVs as compared to IFITM1low/− cells. In contrast, there was no difference in the intensity of EV release between CRC subpopulations with high and low IFITM1 levels. Importantly, the difference in cell proliferation between these two subpopulations disappeared in the presence of fibroblast-derived EVs, proving the functional relevance of the enhanced EV uptake by IFITM1low CRC cells. Furthermore, inactivating IFITM1 resulted in an enhanced EV uptake, highlighting the importance of this molecule in establishing the cellular difference for EV effects. Collectively, we identified CRC cells with functional difference in their EV uptake ability that must be taken into consideration when using EVs as therapeutic tools for targeting cancer cells.

scholarly journals Small extracellular vesicle-encapsulated miR-181b-5p, miR-222-3p and let-7a-5p: Next generation plasma biopsy-based diagnostic biomarkers for inflammatory breast cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250642
Author(s):  
Sarah Hamdy Ahmed ◽  
Nancy A. Espinoza-Sánchez ◽  
Ahmed El-Damen ◽  
Sarah Atef Fahim ◽  
Mohamed A. Badawy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Inflammatory Breast Cancer ◽  
Roc Curves ◽  
Cost Effective ◽  
Extracellular Vesicle ◽  
Lymphatic Invasion ◽  
Precipitation Method ◽  
Liquid Biopsies ◽  
Diagnostic Biomarkers

Inflammatory breast cancer (IBC) is a rare, but aggressive entity of breast carcinoma with rapid dermal lymphatic invasion in young females. It is either poorly or misdiagnosed as mastitis because of the absence of a distinct lump. Small extracellular vesicles (sEVs) circulating in liquid biopsies are a novel class of minimally invasive diagnostic alternative to invasive tissue biopsies. They modulate cancer progression via shuttling their encapsulated cargo including microRNAs (miRNAs) into recipient cells to either trigger signaling or induce malignant transformation of targeted cells. Plasma sEVs < 200 nm were isolated using a modified cost-effective polyethylene glycol (PEG)-based precipitation method and compared to standard methods, namely ultracentrifugation and a commercial kit, where the successful isolation was verified by different approaches. We evaluated the expression levels of selected sEV-derived miR-181b-5p, miR-222-3p and let-7a-5p using quantitative real PCR (qPCR). Relative to non-IBC, our qPCR data showed that sEV-derived miR-181b-5p and miR-222-3p were significantly upregulated, whereas let-7a-5p was downregulated in IBC patients. Interestingly, receiver operating characteristic (ROC) curves analysis revealed that diagnostic accuracy of let-7a-5p alone was the highest for IBC with an area under curve (AUC) value of 0.9188, and when combined with miR-222-3p the AUC was improved to 0.973. Further, 38 hub genes were identified using bioinformatics analysis. Together, circulating sEV-derived miR-181b-5p, miR-222-3p and let-7a-5p serve as promising non-invasive diagnostic biomarkers for IBC.

scholarly journals Blood-Derived Extracellular Vesicle-Associated miR-3182 Detects Non-Small Cell Lung Cancer Patients

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 257
Author(s):  
Kekoolani S. Visan ◽  
Richard J. Lobb ◽  
Shu Wen Wen ◽  
Justin Bedo ◽  
Luize G. Lima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Stage ◽  
Survival Rates ◽  
Cancer Biomarkers ◽  
Extracellular Vesicle ◽  
Lung Cells ◽  
Sequencing Analysis ◽  
Sample Collection ◽  
Liquid Biopsies ◽  
Lung Cancer Patients

With five-year survival rates as low as 3%, lung cancer is the most common cause of cancer-related mortality worldwide. The severity of the disease at presentation is accredited to the lack of early detection capacities, resulting in the reliance on low-throughput diagnostic measures, such as tissue biopsy and imaging. Interest in the development and use of liquid biopsies has risen, due to non-invasive sample collection, and the depth of information it can provide on a disease. Small extracellular vesicles (sEVs) as viable liquid biopsies are of particular interest due to their potential as cancer biomarkers. To validate the use of sEVs as cancer biomarkers, we characterised cancer sEVs using miRNA sequencing analysis. We found that miRNA-3182 was highly enriched in sEVs derived from the blood of patients with invasive breast carcinoma and NSCLC. The enrichment of sEV miR-3182 was confirmed in oncogenic, transformed lung cells in comparison to isogenic, untransformed lung cells. Most importantly, miR-3182 can successfully distinguish early-stage NSCLC patients from those with benign lung conditions. Therefore, miR-3182 provides potential to be used for the detection of NSCLC in blood samples, which could result in earlier therapy and thus improved outcomes and survival for patients.

scholarly journals Advances in the Field of Micro- and Nanotechnologies Applied to Extracellular Vesicle Research: Take-Home Message from ISEV2021

Micromachines ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1563
Author(s):  
Silvia Picciolini ◽  
Francesca Rodà ◽  
Marzia Bedoni ◽  
Alice Gualerzi
Keyword(s):  
Annual Meeting ◽  
Extracellular Vesicles ◽  
International Society ◽  
Biomedical Research ◽  
Human Body ◽  
Knowledge Exchange ◽  
Extracellular Vesicle ◽  
Present Review ◽  
Knowledge Gaps ◽  
Therapeutic Tools

Extracellular Vesicles (EVs) are naturally secreted nanoparticles with a plethora of functions in the human body and remarkable potential as diagnostic and therapeutic tools. Starting from their discovery, EV nanoscale dimensions have hampered and slowed new discoveries in the field, sometimes generating confusion and controversies among experts. Microtechnological and especially nanotechnological advances have sped up biomedical research dealing with EVs, but efforts are needed to further clarify doubts and knowledge gaps. In the present review, we summarize some of the most interesting data presented in the Annual Meeting of the International Society for Extracellular Vesicles (ISEV), ISEV2021, to stimulate discussion and to share knowledge with experts from all fields of research. Indeed, EV research requires a multidisciplinary knowledge exchange and effort. EVs have demonstrated their importance and significant biological role; still, further technological achievements are crucial to avoid artifacts and misleading conclusions in order to enable outstanding discoveries.

scholarly journals Identification of Cancer-Associated Circulating Cells in Anal Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2229 ◽  
Author(s):  
Thomas J. Carter ◽  
Jeyarooban Jeyaneethi ◽  
Juhi Kumar ◽  
Emmanouil Karteris ◽  
Rob Glynne-Jones ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Anal Cancer ◽  
Standard Treatment ◽  
Hpv Infection ◽  
Incidence Rates ◽  
Liquid Biopsies ◽  
Papilloma Virus ◽  
Circulating Cells ◽  
Post Radiation ◽  
Monitoring Treatment

Whilst anal cancer accounts for less than 1% of all new cancer cases, incidence rates have increased by up to 70% in the last 30 years with the majority of cases driven by human papilloma virus (HPV) infection. Standard treatment for localised anal cancer is chemoradiotherapy (CRT). Localised progression is the predominant pattern of relapse but well under 50% of cases are salvaged by surgery, predominantly because confirming recurrence within post-radiation change is very challenging. Identifying cancer-associated circulating cells (CCs) in peripheral blood could offer a corroborative method of monitoring treatment efficacy and identifying relapse early. To study this, nucleated cells were isolated from the blood of patients with anal cancer prior to, during, and after CRT and processed through the Amnis® ImageStream®X Mk II Imaging Flow Cytometer, without prior enrichment, using Pan-cytokeratin (PCK), CD45 antibodies and making use of the DNA dye DRAQ5. Analysis was undertaken using IDEAS software to identify those cells that were PCK-positive and DRAQ5-positive as well as CD45-negative; these were designated as CCs. CCs were identified in 7 of 8 patients; range 60–876 cells per mL of blood. This first report of the successful identification of CCs in anal cancer patients raises the possibility that liquid biopsies will find a future role as a prognostic/diagnostic tool in this patient group.

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