From laboratory to clinic: Translation of extracellular vesicle based cancer biomarkers

Yekula, Anudeep; Muralidharan, Koushik; Kang, Keiko M.; Wang, Lan; Balaj, Leonora; Carter, Bob S.

doi:10.1016/j.ymeth.2020.02.003

Cited by 60 publications

(56 citation statements)

References 74 publications

(89 reference statements)

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“…This technique offers benefits in terms of both diagnostic and therapeutic applications [105]; however, stronger collaborations between microfluidic engineers and clinicians would be able to take advantage of microfluidic technology to isolate EEVs from body fluids [102]. It is well known that EEVs have significant advantages for disease diagnostics and monitoring because of their abundance, stability, and unique molecular cargos [106]. Since the challenges of EEVs' isolation could be addressed by the integration of a microfluidics platform, clinicians must contribute to point-of-care testing and treatment options by focusing on these potential players.…”

Section: Eevs' Isolation Methodsmentioning

confidence: 99%

Cancer Extracellular Vesicles: Next-Generation Diagnostic and Drug Delivery Nanotools

Palazzolo

Memeo²,

Hadla

et al. 2020

Cancers

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Nanosized extracellular vesicles (EVs) with dimensions ranging from 100 to 1000 nm are continuously secreted from different cells in their extracellular environment. They are able to encapsulate and transfer various biomolecules, such as nucleic acids, proteins, and lipids, that play an essential role in cell‒cell communication, reflecting a novel method of extracellular cross-talk. Since EVs are present in large amounts in most bodily fluids, challengeable hypotheses are analyzed to unlock their potential roles. Here, we review EVs by discussing their specific characteristics (structure, formation, composition, and isolation methods), focusing on their key role in cell biology. Furthermore, this review will summarize the biomedical applications of EVs, in particular those between 30 and 150 nm (like exosomes), as next-generation diagnostic tools in liquid biopsy for cancer and as novel drug delivery vehicles.

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Section: Eevs' Isolation Methodsmentioning

confidence: 99%

Cancer Extracellular Vesicles: Next-Generation Diagnostic and Drug Delivery Nanotools

Palazzolo

Memeo²,

Hadla

et al. 2020

Cancers

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“…Various kits based on the above summarized methods have been developed to this end. [ 108 ] From the perspective of developing exosomes for drug delivery, size homogeneity is a crucial property as it will determine the biodistribution of the vesicles. However, the behavior of the exosomes also depends on the tropism caused by superficial molecules in the exosome membrane that are responsible for its vectorization, thus this membrane integrity must also be preserved.…”

Section: Exosomes Isolationmentioning

confidence: 99%

Advances in Exosomes‐Based Drug Delivery Systems

Gutiérrez-Millán

Díaz

Lanao

et al. 2020

Macromolecular Bioscience

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Exosomes, a subgroup of extracellular vesicles, are important mediators of long‐distance intercellular communication and are involved in a diverse range of biological processes such as the transport of lipids, proteins, and nucleic acids. Researchers, seeing the problems caused by the toxic effects and clearance of synthetic nanoparticles, consider exosomes as an interesting alternative to such nanoparticles in the specific and controlled transport of drugs. In recent years, there have been remarkable advances in the use of exosomes in cancer therapeutics or for treating neurological diseases, among other applications. The objective of this work is to analyze studies focused on exosomes used in drug delivery system, present and future applications in this field of research are discussed based on the results obtained.

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“…These aspects are extensively reviewed elsewhere. [151,161,162] Ideally, an advanced machine learning model [163,164] integrating clinical, imaging and liquid biopsy based molecular characterization could help decision making during follow-up (Figure 1b). With the advent of sensitive technologies, liquid biopsy could be the future of tumor diagnosis, monitoring, and therapy response.…”

Section: Future Directionsmentioning

confidence: 99%

Liquid Biopsy Strategies to Distinguish Progression from Pseudoprogression and Radiation Necrosis in Glioblastomas

et al. 2020

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despite aggressive treatment. [1] Currently, maximal resection followed by radiation therapy with concurrent temozolomide (TMZ) and adjuvant TMZ treatment is the standard of care. Post-treatment surveillance involves serial MRI. A challenge faced by clinicians is the diagnosis and management of a gadolinium enhancing lesion on a follow-up MRI post-treatment. This suspicious lesion could be progressive disease (PD) or a mere post-treatment radiation effects such as pseudoprogression or radiation necrosis (RN). Pseudoprogression and RN are distinct clinical entities, which when identified and managed appropriately result in better outcomes, while PD of the tumor is often dismal. Patients with PD have a median survival of 3-6 months, [2] and there is no standard of care. Systemic options include TMZ rechallenge, lomustine, and antiangiogenic therapy such as bevacizumab, but their effectiveness is limited. Reradiation and reresection can be considered depending on the location of the tumor and the condition of the patient. [3] Conversely, antiangiogenic drugs like bevacizumab or cediranib decrease contrast enhancement by altering permeability of tumor vasculature without actual reduction in tumor burden, referred to as pseudoresponse. Distinguishing these clinical entities from PD is crucial to avoid unnecessary reoperations, premature discontinuation of adjuvant TMZ or its substitution with second line agents. MR imaging based monitoring is the current standard of care for post-surgical monitoring. Contrast enhancement on imaging is indicative of disrupted blood brain barrier (BBB), but not tumor presence. [4] Currently, MRI-based Response Assessment in Neuro-Oncology (RANO) criteria is used to monitor treatment response in GBM patients. The criteria included T1 gadolinium enhancing disease, T2/FLAIR changes, new lesions, corticosteroid use, and clinical status. [5] Adoption of RANO criteria for monitoring response is not without limitations. There is ambiguity in identifying radiation effects, enrolling patients into clinical trials and monitoring immunotherapy response. [6] Advanced imaging modalities including diffusion-tensor imaging, perfusion imaging, MR spectroscopy (MRS), and positron emission tomography (PET) imaging Liquid biopsy for the detection and monitoring of central nervous system tumors is of significant clinical interest. At initial diagnosis, the majority of patients with central nervous system tumors undergo magnetic resonance imaging (MRI), followed by invasive brain biopsy to determine the molecular diagnosis of the WHO 2016 classification paradigm. Despite the importance of MRI for long-term treatment monitoring, in the majority of patients who receive chemoradiation therapy for glioblastoma, it can be challenging to distinguish between radiation treatment effects including pseudoprogression, radiation necrosis, and recurrent/progressive disease based on imaging alone. Tissue biopsy-based monitoring is high risk and not always feasible. However, distinguishing these entities is of critical im...

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From laboratory to clinic: Translation of extracellular vesicle based cancer biomarkers

Cited by 60 publications

References 74 publications

Cancer Extracellular Vesicles: Next-Generation Diagnostic and Drug Delivery Nanotools

Cancer Extracellular Vesicles: Next-Generation Diagnostic and Drug Delivery Nanotools

Advances in Exosomes‐Based Drug Delivery Systems

Liquid Biopsy Strategies to Distinguish Progression from Pseudoprogression and Radiation Necrosis in Glioblastomas

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