scholarly journals Small Extracellular Vesicles: A Novel Avenue for Cancer Management

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanan Gao ◽  
You Qin ◽  
Chao Wan ◽  
Yajie Sun ◽  
Jingshu Meng ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Extracellular Vesicles ◽  
Anticancer Agents ◽  
Early Stage ◽  
Cell Types ◽  
The United States ◽  
Extracellular Vesicle ◽  
Cancer Therapies ◽  
Clinical Implementation ◽  
Cancer Management

Extracellular vesicles are small membrane particles derived from various cell types. EVs are broadly classified as ectosomes or small extracellular vesicles, depending on their biogenesis and cargoes. Numerous studies have shown that EVs regulate multiple physiological and pathophysiological processes. The roles of small extracellular vesicles in cancer growth and metastasis remain to be fully elucidated. As endogenous products, small extracellular vesicles are an ideal drug delivery platform for anticancer agents. However, several aspects of small extracellular vesicle biology remain unclear, hindering the clinical implementation of small extracellular vesicles as biomarkers or anticancer agents. In this review, we summarize the utility of cancer-related small extracellular vesicles as biomarkers to detect early-stage cancers and predict treatment outcomes. We also review findings from preclinical and clinical studies of small extracellular vesicle-based cancer therapies and summarize interventional clinical trials registered in the United States Food and Drug Administration and the Chinese Clinical Trials Registry. Finally, we discuss the main challenges limiting the clinical implementation of small extracellular vesicles and recommend possible approaches to address these challenges.

scholarly journals Emerging techniques in the isolation and characterization of extracellular vesicles and their roles in cancer diagnostics and prognostics

The Analyst ◽  
2016 ◽  
Vol 141 (2) ◽  
pp. 371-381 ◽  
Author(s):  
Vijaya Sunkara ◽  
Hyun-Kyung Woo ◽  
Yoon-Kyoung Cho
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Diagnostics ◽  
Clinical Implementation ◽  
Characterization Methods ◽  
Cancer Management ◽  
Isolation And Characterization

We present an overview of current isolation, detection, and characterization methods of extracellular vesicles and their applications and limitations as a potential emerging biomarker in cancer management and their clinical implementation.

Updates in the management and future landscape of urothelial carcinoma

2020 ◽  
pp. 107815522097102
Author(s):  
Kirollos S Hanna ◽  
Maren Campbell ◽  
Adam Kolling ◽  
Alex Husak ◽  
Sabrina Sturm ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Urothelial Carcinoma ◽  
Metastatic Disease ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Locally Advanced ◽  
The United States ◽  
Cancer Type ◽  
Antibody Drug Conjugate ◽  
Early Stage Disease

Urothelial carcinoma is the sixth most common cancer type in the United States. Although most patients present with early stage disease which is associated with improved outcomes, many will progress to locally advanced or metastatic disease. Immune checkpoint inhibitors have significantly impacted the treatment paradigm for patients and have resulted in improved survival rates. Despite their proven efficacy, many ongoing clinical trials continue to refine combinations with chemotherapy, sequencing of therapies and the role of ligand expression. Additionally, novel targets have been identified for advanced urothelial carcinoma and have led to the approval of the antibody-drug conjugate, enfortumab vedotin, and the fibroblast growth factor receptor-targeted, erdafitinib. Enrollment in a clinical trial is strongly encouraged for all stages of advanced or metastatic disease. Numerous ongoing clinical trials are likely to impact the treatment armamentarium for patients. In this manuscript, we highlight key updates in the clinical management for patients and outline ongoing trials.

scholarly journals Cancer associated-fibroblast-derived exosomes in cancer progression

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chao Li ◽  
Adilson Fonseca Teixeira ◽  
Hong-Jian Zhu ◽  
Peter ten Dijke
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Chemotherapy Resistance ◽  
Cell Types ◽  
Cancer Therapies ◽  
Cancer Associated Fibroblast

AbstractTo identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years in particular with the advent of clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists of multiple cell types that are embedded in the extracellular matrix (ECM), including immune cells, endothelial cells and cancer associated fibroblasts (CAFs), which communicate with cancer cells and each other during tumor progression. CAFs are a dominant and heterogeneous cell type within the TME with a pivotal role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis and chemotherapy resistance. CAFs mediate their effects in part by remodeling the ECM and by secreting soluble factors and extracellular vesicles. Exosomes are a subtype of extracellular vesicles (EVs), which contain various biomolecules such as nucleic acids, lipids, and proteins. The biomolecules in exosomes can be transmitted from one to another cell, and thereby affect the behavior of the receiving cell. As exosomes are also present in circulation, their contents can also be explored as biomarkers for the diagnosis and prognosis of cancer patients. In this review, we concentrate on the role of CAFs-derived exosomes in the communication between CAFs and cancer cells and other cells of the TME. First, we introduce the multiple roles of CAFs in tumorigenesis. Thereafter, we discuss the ways CAFs communicate with cancer cells and interplay with other cells of the TME, and focus in particular on the role of exosomes. Then, we elaborate on the mechanisms by which CAFs-derived exosomes contribute to cancer progression, as well as and the clinical impact of exosomes. We conclude by discussing aspects of exosomes that deserve further investigation, including emerging insights into making treatment with immune checkpoint inhibitor blockade more efficient.

scholarly journals Recent Advances in Extracellular Vesicles as Drug Delivery Systems and Their Potential in Precision Medicine

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1006 ◽  
Author(s):  
Bart de Jong ◽  
Eric Raul Barros ◽  
Joost G. J. Hoenderop ◽  
Juan Pablo Rigalli
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Early Stage ◽  
Treatment Options ◽  
Cell Types ◽  
Administration Routes ◽  
The Individual ◽  
Key Steps

Extracellular vesicles (EVs) are membrane-bilayered nanoparticles released by most cell types. Recently, an enormous number of studies have been published on the potential of EVs as carriers of therapeutic agents. In contrast to systems such as liposomes, EVs exhibit less immunogenicity and higher engineering potential. Here, we review the most relevant publications addressing the potential and use of EVs as a drug delivery system (DDS). The information is divided based on the key steps for designing an EV-mediated delivery strategy. We discuss possible sources and isolation methods of EVs. We address the administration routes that have been tested in vivo and the tissue distribution observed. We describe the current knowledge on EV clearance, a significant challenge towards enhancing bioavailability. Also, EV-engineering approaches are described as alternatives to improve tissue and cell-specificity. Finally, a summary of the ongoing clinical trials is performed. Although the application of EVs in the clinical practice is still at an early stage, a high number of studies in animals support their potential as DDS. Thus, better treatment options could be designed to precisely increase target specificity and therapeutic efficacy while reducing off-target effects and toxicity according to the individual requirements of each patient.

scholarly journals Extracellular Vesicles as Biomarkers and Therapeutic Tools: From Pre-Clinical to Clinical Applications

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 359
Author(s):  
Maria Chiara Ciferri ◽  
Rodolfo Quarto ◽  
Roberta Tasso
Keyword(s):  
Clinical Trials ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cell Types ◽  
Storage Conditions ◽  
Clinical Applications ◽  
The Other ◽  
The Past ◽  
Therapeutic Tools ◽  
And Storage

Extracellular vesicles (EVs) are ubiquitous masters of intercellular communication, being detectable in tissues, circulation, and body fluids. Their complex cargo reflects the (patho)physiologic status of the cells from which they originate. Due to these properties, the potential of EVs, and in particular exosomes, to serve as biomarkers or therapeutics has grown exponentially over the past decade. On one side, numerous studies have demonstrated that EV-associated nucleic acids and proteins are implicated in cancer progression, as well as neurodegenerative, infectious, and autoimmune disorders. On the other, the therapeutic use of EVs secreted by various cell types, and in particular stem/progenitor cells, present significant advantages in comparison to the corresponding parental cells, such as the less complex production and storage conditions. In this review, we examine some of the major pre-clinical studies dealing with EVs and exosomes, that led to the development of numerous completed clinical trials.

scholarly journals Emerging strategies to bridge the gap between pharmacogenomic research and its clinical implementation

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Volker M. Lauschke ◽  
Magnus Ingelman-Sundberg
Keyword(s):  
Clinical Trials ◽  
Drug Response ◽  
Clinical Decision Making ◽  
Rare Variants ◽  
Clinical Importance ◽  
Clinical Decision ◽  
The United States ◽  
Added Value ◽  
Therapeutic Drug ◽  
Clinical Implementation

AbstractThe genomic inter-individual heterogeneity remains a significant challenge for both clinical decision-making and the design of clinical trials. Although next-generation sequencing (NGS) is increasingly implemented in drug development and clinical trials, translation of the obtained genomic information into actionable clinical advice lags behind. Major reasons are the paucity of sufficiently powered trials that can quantify the added value of pharmacogenetic testing, and the considerable pharmacogenetic complexity with millions of rare variants with unclear functional consequences. The resulting uncertainty is reflected in inconsistencies of pharmacogenomic drug labels in Europe and the United States. In this review, we discuss how the knowledge gap for bridging pharmacogenomics into the clinics can be reduced. First, emerging methods that allow the high-throughput experimental characterization of pharmacogenomic variants combined with novel computational tools hold promise to improve the accuracy of drug response predictions. Second, tapping of large biobanks of therapeutic drug monitoring data allows to conduct high-powered retrospective studies that can validate the clinical importance of genetic variants, which are currently incompletely characterized. Combined, we are confident that these methods will improve the accuracy of drug response predictions and will narrow the gap between variant identification and its utilization for clinical decision-support.

scholarly journals Extracellular vesicles: communication, coercion, and conditioning

2013 ◽  
Vol 24 (9) ◽  
pp. 1253-1259 ◽  
Author(s):  
David A. Shifrin ◽  
Michelle Demory Beckler ◽  
Robert J. Coffey ◽  
Matthew J. Tyska
Keyword(s):  
Extracellular Vesicles ◽  
Extracellular Space ◽  
Cell Biology ◽  
Biological Significance ◽  
Local Environment ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Functional Studies ◽  
Wide Range ◽  
Physiological Homeostasis

Cells communicate with neighboring cells and condition their local environment by secreting soluble factors into the extracellular space. These well-studied facets of cell biology are essential for the establishment and maintenance of physiological homeostasis. However, accumulating evidence has revealed that specific ligands, enzymes, and macromolecules are distributed into the extracellular space by virtue of their association with small vesicles, which are released by a variety of cell types. Although the biological significance of such vesicles was initially debated, purification and subsequent functional studies have shown that these extracellular vesicles are bioactive organelles carrying a wide range of protein and nucleic acid cargoes. In many cases these vesicles are laden with molecules that are involved in cell signaling, although other diverse functions are being revealed at a rapid pace. In this Perspective, we discuss recent developments in the understanding of the major pathways of extracellular vesicle biogenesis and how these vesicles contribute to the maintenance of physiological homeostasis.

scholarly journals Cancer Cell Membrane-Coated Nanoparticles for Cancer Management

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1836 ◽  
Author(s):  
Jenna C. Harris ◽  
Mackenzie A. Scully ◽  
Emily S. Day
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Treatment Success ◽  
Cancer Therapies ◽  
Clinical Implementation ◽  
Cancer Management ◽  
Coated Nanoparticles ◽  
Self Recognition ◽  
Natural Cell

Cancer is a global health problem in need of transformative treatment solutions for improved patient outcomes. Many conventional treatments prove ineffective and produce undesirable side effects because they are incapable of targeting only cancer cells within tumors and metastases post administration. There is a desperate need for targeted therapies that can maximize treatment success and minimize toxicity. Nanoparticles (NPs) with tunable physicochemical properties have potential to meet the need for high precision cancer therapies. At the forefront of nanomedicine is biomimetic nanotechnology, which hides NPs from the immune system and provides superior targeting capabilities by cloaking NPs in cell-derived membranes. Cancer cell membranes expressing “markers of self” and “self-recognition molecules” can be removed from cancer cells and wrapped around a variety of NPs, providing homotypic targeting and circumventing the challenge of synthetically replicating natural cell surfaces. Compared to unwrapped NPs, cancer cell membrane-wrapped NPs (CCNPs) provide reduced accumulation in healthy tissues and higher accumulation in tumors and metastases. The unique biointerfacing capabilities of CCNPs enable their use as targeted nanovehicles for enhanced drug delivery, localized phototherapy, intensified imaging, or more potent immunotherapy. This review summarizes the state-of-the-art in CCNP technology and provides insight to the path forward for clinical implementation.

Availability of Experimental Therapy Outside Oncology Randomized Clinical Trials in the United States

2010 ◽  
Vol 28 (34) ◽  
pp. 5067-5073 ◽  
Author(s):  
Erika P. Hamilton ◽  
Gary H. Lyman ◽  
Jeffrey Peppercorn
Keyword(s):  
United States ◽  
Clinical Trials ◽  
English Language ◽  
Randomized Clinical Trials ◽  
The United States ◽  
Phase Iii ◽  
Experimental Therapy ◽  
Cancer Therapies ◽  
Medline Search ◽  
Grade 3

Purpose Investigational cancer therapies may be available outside trials as “off-protocol therapy” (OPRx), with implications for patient safety, trial accrual, and access to care. We conducted a literature-based analysis of recent randomized trials to evaluate the potential scope and impact of OPRx in the United States. Methods A MEDLINE search identified all English-language phase III medical oncology randomized clinical trials (RCTs) published over a 2-year period ending April 17, 2008. Determination of OPRx availability was based on US Food and Drug Administration approval for any indication. We limited assessment of accrual to studies with US sites. Data from articles were extracted independently by two investigators. Results Among 172 eligible RCTs, the majority (108; 63%) evaluated drugs that were available OPRx in the United States at trial initiation, while an additional 19 (11%) evaluated interventions that became available during the trial. Among trials with US sites, time to accrual was slower (41 vs 22 months; P = .002) and less efficient (8.8 v 22.7 patients per month; P = .001) when OPRx was available. Sixty-six percent of RCTs reported at least one increased grade 3 to 4 toxicity in the experimental arm, 47% reported superior efficacy for at least one major clinical outcome in the experimental arm, and 27% reported improvement in overall survival. These outcomes did not vary on the basis of OPRx availability. Conclusion The majority of recent oncology RCTs involve experimental interventions that are available outside trials in the United States with potential impact on trial accrual. The safety and efficacy of novel interventions must be determined by clinical trials.

scholarly journals Extracellular Vesicles as Biomarkers Carriers in Bladder Cancer: Diagnosis, Surveillance, and Treatment

2021 ◽  
Vol 22 (5) ◽  
pp. 2744
Author(s):  
Natalia Georgantzoglou ◽  
Alexandros Pergaris ◽  
Christos Masaoutis ◽  
Stamatios Theocharis
Keyword(s):  
Bladder Cancer ◽  
Extracellular Vesicles ◽  
Developed Countries ◽  
Extracellular Vesicle ◽  
Disease Stage ◽  
Bladder Cancer Patient ◽  
Sample Collection ◽  
Bladder Tissue ◽  
Tissue Samples ◽  
Cancer Management

Exosomes are extracellular vesicles, enriched in biomolecular cargo consisting of nucleic acids, proteins, and lipids, which take part in intercellular communication and play a crucial role in both physiologic functions and oncogenesis. Bladder cancer is the most common urinary malignancy and its incidence is steadily rising in developed countries. Despite the high five-year survival in patients diagnosed at early disease stage, survival substantially drops in patients with muscle-invasive or metastatic disease. Therefore, early detection of primary disease as well as recurrence is of paramount importance. The role that exosomal biomarkers could play in bladder cancer patient diagnosis and surveillance, as well as their potential therapeutic applications, has not been extensively studied in this malignancy. In the present review, we summarize all relevant data obtained so far from cell lines, animal models, and patient biofluids and tissues. Current literature suggests that urine is a rich source of extracellular vesicle-derived biomarkers, compared with blood and bladder tissue samples, with potential applications in bladder cancer management. Further studies improving sample collection procedures and optimizing purification and analytical methods should augment bladder cancer diagnostic, prognostic, and therapeutic input of extracellular vesicles biomarkers in the future.

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