Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The precursor of CRC is a colorectal polyp, of which adenoma is the most common histological type. The initial step in CRC development is the gradual accumulation of a series of genetic and epigenetic alterations in the normal colonic epithelium. Genetic alterations play a major role in a subset of CRCs, but the pathophysiological contribution of epigenetic aberrations has recently attracted attention. Epigenetic marks occur early in cancer pathogenesis and are therefore important molecular hallmarks of cancer. This makes some epigenetic alterations clinically relevant for early detection not only of CRC but also of precancerous polyps. In this review we focus on three types of non-coding RNAs as epigenetic regulators: miRNA, lncRNA, and lncRNAs, highlighting their biomarker potential.

Circulating tumor DNA (ctDNA) analysis has emerged as a minimally invasive tool for detecting minimal residual disease (MRD) in colorectal cancer (CRC) patients. This enables dynamic risk stratification, earlier recurrence detection and optimized post-surgical treatment. Two primary methodologies have been developed for ctDNA-based MRD detection: tumor-informed strategies, which identify tumor-specific mutations through initial tissue sequencing to guide ctDNA monitoring, and tumor-agnostic approaches, which utilize predefined panels to detect common cancer-associated genomic or epigenomic alterations directly from plasma without prior tissue analysis. The debate over which is superior in terms of sensitivity, specificity, cost-effectiveness and clinical feasibility remains unsolved.

This review summarizes studies published up to November 2024, exploring the utility and performance of tumor-informed and tumor-agnostic approaches for ctDNA analysis in CRC. We evaluate the strengths and limitations of each methodology, focusing on sensitivity, specificity and clinical outcomes.

Both strategies demonstrate clinical utility in post-operative risk stratification and guiding adjuvant chemotherapy decisions in CRC patients. Tumor-informed approaches generally exhibit superior sensitivity and specificity for recurrence prediction, attributed to their personalized tumor profile designs. However, these methods are limited by the need for prior tissue sequencing and higher associated costs. In contrast, tumor-agnostic approaches offer broader applicability due to their reliance on plasma-only analysis, although with relatively lower sensitivity. Technological advancements, including fragmentomics and multi-omic integrations, are expanding the capabilities of ctDNA-based MRD detection, enhancing the performance of both approaches.

While tumor-informed strategies currently offer higher precision in MRD detection, tumor-agnostic approaches are gaining traction due to their convenience and improving performance metrics. The integration of novel technologies in ongoing clinical trials may redefine the optimal approach for MRD detection in CRC, paving the way for more personalized and adaptive patient management strategies.

Exosomes can be modified and designed for various therapeutic goals because of their unique physical and chemical characteristics. Researchers have identified tumor-derived exosomes (TEXs) as significant players in cancer by influencing tumor growth, immune response evasion, angiogeneis, and drug resistance. TEXs promote the production of specific proteins important for cancer progression. Due to their easy accessibility, TEXs are being modified through genetic, drug delivery, membrane, immune system, and chemical alterations to be repurposed as vehicles for delivering drugs to improve cancer treatment outcomes. In the complex in vivo environment, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) system encounters challenges from degradation, neutralization, and immune responses, emphasizing the need for strategic distribution strategies for effective genome editing. Engineered exosomes present a promising avenue for delivering CRISPR/Cas9 in vivo. In this review, we will explore different techniques for enhancing TEXs using various engineering strategies. Additionally, we will discuss how these exosomes can be incorporated into advanced genetic engineering systems like CRISPR/Cas9 for possible therapeutic uses.

Extracellular vesicles (EVs) represent a diverse class of nanoscale membrane vesicles actively released by cells. These EVs can be further subdivided into categories like exosomes and microvesicles, based on their origins, sizes, and physical attributes. Significantly, disease-derived EVs have been detected in virtually all types of body fluids, providing a comprehensive molecular profile of their cellular origins. As a result, EVs are emerging as a valuable addition to liquid biopsy techniques. In this collective statement, the authors share their current perspectives on EV-related research and product development, with a shared commitment to translating this newfound knowledge into clinical applications for cancer and other diseases, particularly as disease biomarkers. The consensus within this document revolves around the overarching recognition of the merits, unresolved questions, and existing challenges surrounding EVs. This consensus manuscript is a collaborative effort led by the Committee of Exosomes, Society of Tumor Markers, Chinese anti-Cancer Association, aimed at expediting the cultivation of robust scientific and clinically applicable breakthroughs and propelling the field forward with greater swiftness and efficacy.

Background: Liquid biopsy has gained significant attention as a non-invasive method for cancer detection and monitoring. IsomiRs and tRNA-derived fragments (tRFs) are small non-coding RNAs that arise from non-canonical microRNA (miRNAs) processing and the cleavage of tRNAs, respectively. These small non-coding RNAs have emerged as pro-mising cancer biomarkers, and their distinct expression patterns highlight the need for further exploration of their roles in cancer research. Methods: In this study, we investigated the differential expression profiles of miRNAs, isomiRs, and tRFs in plasma extracellular vesicles (EVs) from colorectal and prostate cancer patients compared to healthy controls. Subsequently, a combinatorial analysis using the CombiROC package was performed to identify a panel of biomarkers with optimal diagnostic accuracy. Results: Our results demonstrate that a combination of miRNAs, isomiRs, and tRFs can effectively di- stinguish cancer patients from healthy controls, achieving accuracy and an area under the curve (AUC) of approximately 80%. Conclusions: These findings highlight the potential of a combinatorial approach to small RNA analysis in liquid biopsies for improved cancer diagnosis and management.

Colorectal cancer is a common and fatal disease that affects many people globally. CRC is classified as the third most prevalent cancer among males and the second most frequent cancer among females worldwide. The purpose of this article is to examine how personalized medicine might be used to treat colorectal cancer. The classification of colorectal cancer based on molecular profiling, including the detection of significant gene mutations, genomic instability, and gene dysregulation, is the main topic of this discussion. Advanced technologies and biomarkers are among the detection methods that are explored, demonstrating their potential for early diagnosis and precise prognosis. In addition, the essay explores the world of treatment possibilities by providing light on FDA-approved personalized medicine solutions that provide individualized and precise interventions based on patient characteristics. This article assesses targeted treatments like cetuximab and nivolumab, looks at the therapeutic usefulness of biomarkers like microsatellite instability (MSI) and circulating tumor DNA (ctDNA), and investigates new approaches to combat resistance. Through this, our review provides a thorough overview of personalized medicine in the context of colorectal cancer, ultimately highlighting its potential to revolutionize the field and improve patient care.

Patients with colorectal cancer (CRC) have a higher chance of survival when the disease is detected and treated effectively at an early stage. Plasmacytoma variant translocation 1 (PVT-1), an oncogenic lncRNA, and neuroblastoma associated trans-cript 1 (NBAT1), a tumor suppressor lncRNA, have been linked to CRC progression, acting as competing endo-genous RNAs to the tumor suppressor miRNA-145 and oncomiRNA-21. The aim of the current study was to construct a competing endogenous RNA (ceRNA) associated with CRC. In addition, we aimed to investigate the impact of single nucleotide polymorphisms in the rs13255292 lncRNA PVT-1 on miR-145 expression levels and the lncRNA-NBAT1/miR-21 axis in the progression of CRC.

Bioinforma-tic analysis was performed to determine differentially expressed genes (DEGs), differentially expressed micro-RNAs (DEMs), and differentially expressed lncRNAs (DELs) in CRC. PVT-1 rs13255292 C/T was genotyped and serum PVT-1, NBAT-1, miRNA-145 and miRNA-21 were assessed by qPCR in 85 CRC patients, 80 AP, and 85 controls.

The frequencies of the PVT-1 rs13255292 CT/TT genotype and T al-le-- le were significantly elevated in the CRC group compared to the controls. PVT-1 serum levels significantly increased due to the presence of the T allele in the studied groups, which was associated with downregulation of the miR-145 tumor suppressor. Also, the expression of NBAT-1 was significantly down-expressed, while that of oncomiR-21 was significantly elevated.

Bioinformatics analyses provides effective identification of potential lncRNAs linked with CRC. PVT-1/miR-145 and NBAT1/miR-21 are being investigated as potential non-invasive diagnostic biomarkers for CRC.

Detection of microRNAs (miRNAs) in the serum is an effective liquid biopsy technique for cancer diagnosis. However, conventional diagnostic methods are time-consuming and complex. Therefore, in this study, we established a signaling probe-based DNA microarray system for miRNA detection. PCR, fluorescence labeling, and washing are not necessary for signaling probes. Four probes were designed using different miRNAs as diagnostic cancer markers. The developed system is useful for various miRNAs, regardless of their target lengths (18-26-mer) and GC content (36%-89%). Here, all the assays were performed within 40 min. Overall, our signaling probe-based DNA hybridization system facilitates the simple and rapid detection of serum miRNAs without the need for gene amplification, fluorescence labeling and washing.

Cancer cells are among the many types of cells that release exosomes, which are nanovesicles. Because of their many potential applications, exosomes have recently garnered much attention from cancer researchers. The bioactive substances that exosomes release as cargo have been the subject of several investigations. The substances in question may operate as biomarkers for diagnosis or affect apoptosis, the immune system, the development and spread of cancer, and other processes. Others have begun to look at exosomes in experimental therapeutic trials because they believe they may be useful in the treatment of cancer. This review started with a short description of exosome biogenesis and key features. Next, the potential of tumor-derived exosomes and oncosomes to influence the immune system throughout the development of cancer, as well as alter tumor microenvironments (TMEs) and pre-metastatic niche creation, was investigated. Finally, there was talk of exosomes' possible use in cancer treatment. Furthermore, there is emerging consensus about the potential application of exosomes to be biological reprogrammers of cancer cells, either as carriers of naturally occurring chemicals, including anticancer medications, or as carriers of anticancer vaccines for immunotherapy as well as boron neutron capture therapy (BNCT). We briefly review the key ideas and logic behind this intriguing therapy recommendation.

Exosomes are a member of extracellular vesicles. However, their biological characteristics differ from those of other vesicles, and recently, their powerful functions as information molecules, biomarkers, and carriers have been demonstrated. Malignancies are the leading cause of high morbidity and mortality worldwide. The cure rate of malignancies can be improved by improving early screening rates and therapy. Moreover, a close correlation between exosomes and malignancies has been observed. An in-depth study of exosomes can provide new methods for diagnosing and treating tumors. Therefore, this study aimed to review, sort, and summarize such achievements, and present ideas and opinions on the application of exosomes in tumor treatment.

Exosomal microRNAs (exomiRs) play a critical role in intercellular communication, especially in cancer, where they regulate key cellular processes like proliferation, angiogenesis, and metastasis, highlighting their significance as potential diagnostic and therapeutic targets. Here, we aimed to characterize the role of exomiRs, derived from seven cancer types (four cell lines and three tumors), in influencing the pre-metastatic niche (PMN). In each cancer type we extracted high confidence exomiRs (LogFC >= 2 in exosomes relative to control), their experimentally validated targets, and the enriched pathways among those targets. We then selected the top100 high-confidence targets based on their frequency of appearance in the enriched pathways. We observed significantly higher GC content in exomiRs relative to genomic background. Gene Ontology analysis revealed both general cancer processes, such as wound healing and epithelial cell proliferation, as well as cancer-specific processes, such as "angiogenesis" in the kidney and "ossification" in the lung. ExomiR targets were enriched for cancer-specific tumor suppressor genes and downregulated in PMN formed in lungs compared to normal. Motif analysis showed high inter-cancer similarity among motifs enriched in exomiRs. Our analysis recapitulated exomiRs associated with M2 macrophage differentiation and chemoresistance, such as miR-21 and miR-222-3p, regulating signaling pathways like PTEN/PI3/Akt, NF-kB, etc. Additionally, Cox regression analysis in TCGA indicated that exomiR targets are significantly associated with better overall survival of patients. Lastly, support vector machine model using exomiR targets gene expression classified responders and non-responders to therapy with an AUROC ranging from 0.72 to 0.96, higher than previously reported gene signatures.

The accurate diagnosis of non-obstructive azoospermia and obstructive azoospermia is crucial for selecting appropriate clinical treatments. This study aimed to investigate the pivotal role of microRNAs in circulating plasma extracellular vesicles in distinguishing between non-obstructive azoospermia and obstructive azoospermia, as well as uncovering the signaling pathways involved in azoospermia pathogenesis. In this study, differential expression of extracellular vesicle miR-513c-5p and miR-202-5p was observed between non-obstructive azoospermia and obstructive azoospermia patients, while the selenocompound metabolism pathway could be affected in azoospermia through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The predictive power of these microRNAs was evaluated using receiver characteristic operator-area under the curve analysis, demonstrating promising sensitivity, specificity, and area under the curve values. A binomial regression equation incorporating circulating plasma levels of extracellular vesicles miR-202-5p and miR-513c-5p along with follicle-stimulating hormone was calculated to provide a clinically applicable method for diagnosing non-obstructive azoospermia and obstructive azoospermia. This study presents a potentially non-invasive testing approach for distinguishing between non-obstructive azoospermia and obstructive azoospermia, offering a possibly valuable tool for clinical practice.

Extracellular vesicles (EVs) composed of various biologically active constituents, such as proteins, nucleic acids, lipids, and metabolites, have emerged as a noteworthy mode of intercellular communication. There are several categories of EVs, including exosomes, microvesicles, and apoptotic bodies, which largely differ in their mechanisms of formation and secretion. The amount of evidence indicated that changes in the EV quantity and composition play a role in multiple aspects of cancer development, such as the transfer of oncogenic signals, angiogenesis, metabolism remodeling, and immunosuppressive effects. As EV isolation technology and characteristics recognition improve, EVs are becoming more commonly used in the early diagnosis and evaluation of treatment effectiveness for cancers. Actually, EVs have sparked clinical interest in their potential use as delivery vehicles or vaccines for innovative antitumor techniques. This review will focus on the function of biological molecules contained in EVs linked to cancer progression and their participation in the intricate interrelationship within the tumor microenvironment. Furthermore, the potential efficacy of an EV-based liquid biopsy and delivery cargo for treatment will be explored. Finally, we explicitly delineate the limitations of EV-based anticancer therapies and provide an overview of the clinical trials aimed at improving EV development.

Preeclampsia (PE) is a critical and severe disease in obstetrics, which seriously affects maternal and neonatal life safety and long-term prognosis. However, the etiology and pathogenesis of PE are complex, and no unified conclusion has been reached. The types and number of exosomes and their transport substances in PE patients changed. The study of exosomes in PE patients helps clarify the etiology, diagnosis, effective treatment, accurate monitoring, and prognosis.

The published articles were reviewed.

Exosomes may affect endothelial and vascular production and function, participate in maternal-fetal immune regulation, and transport substances such as miRNAs, lncRNAs, and proteins involved in the development of PE. Detection of the contents of exosomes can help in the early diagnosis of PE, and can help to improve PE by inhibiting the action of exosomes or preventing their binding to target organs.

Exosomes may be involved in the development of PE, and exosomes can be used as markers for predicting the onset of PE and tracking the disease process and determining the prognosis, and exosomes have great potential in the treatment of PE.

Liquid biopsy has an underexplored diagnostic potential in colorectal cancer (CRC). Sufficient quantity and quality of its elements (circulating cell-free DNA (ccfDNA), exosomes and exosomal RNA) are essential for accurate results. The present study aims to establish the optimal protocol for handling liquid biopsy samples. Samples were obtained by collecting peripheral blood from colorectal adenoma patients in CellSave tubes. Plasma was separated within six hours using differential centrifugation and aliquots stored at - 20/- 80 °C until further processing. Three methods for isolation of ccfDNA, and two combinations of kits for isolation of exosomes and exosomal RNA were tested. The quality and quantity of ccfDNA isolates were evaluated. Exosomes were characterised by determining size, concentration, and total and specific protein content. Expression of chosen microRNAs, miR-19a-3p and miR-92-3p, which have been implicated in CRC progression, were determined. The vacuum-column-based kit showed the highest quantities of isolated ccfDNA (P-value < 0.001). Kits for exosome isolation significantly differed in size (P-value = 0.016), concentration (P-value = 0.016) and protein content (P-value = 0.016). There was no significant difference in expressions of miR-19a-3p (P-value = 0.219) and miR-92a-3p (P-value = 0.094) between the two isolation kits. The new, adapted protocol described, enables simultaneous analysis of multiple elements when investigating potential biomarkers of CRC.

Extracellular vesicles (EVs), the ubiquitous part of human biology, represent a small heterogenous, membrane-enclosed body that contains a diverse payload including genetic materials in the form of DNA, RNAs, small non-coding RNAs, etc. mostly mirroring their source of origin. Since, a vast majority of research has been conducted on how nucleic acids, proteins, lipids, and metabolites, associated with EVs can be effectively utilized to identify disease progression and therapeutic responses in cancer patients, EVs are increasingly being touted as valuable and reliable identifiers of cancer biomarkers in liquid biopsies. However, the lack of comprehensive clinical validation and effective standardization protocols severely limits its applications beyond the laboratories. The present review focuses on understanding the role of circulating EVs in different cancers and how they could potentially be treated as cancer biomarkers, typically due to the presence of bioactive molecules such as small non-coding RNAs, RNAs, DNA, proteins, etc., and their utilization for fine-tuning therapies. Here, we provide a brief general biology of EVs including their classification and subsequently discuss the source of circulatory EVs, the role of their associated payload as biomarkers, and how different cancers affect the level of circulatory EVs population.

The challenges associated with liquid biopsy of colorectal cancer (CRC) are closely linked to the substantial variations observed in gene expression profiles among patients. This variability complicates the selection of an ideal biomarker for accurate diagnosis. In this report, we propose that employing a combination of miRNAs offers a better change for enhancing the accuracy of CRC diagnosis compared to solely relying on single miRNAs. As an illustrative example, we measured 9 miRNAs from 45 patient samples (comprising 31 CRC cases and 14 healthy controls) via RT-qPCR. We then utilized two methods: (1) LASSO regression for marker ranking and (2) linear discriminant analysis (LDA) to identify the optimal weighted combination of multiple markers. Our data indicates that combination of triple markers, selected based on their ranking, exhibited the highest diagnostic performance, including a sensitivity of 93.6% (95% confidence interval, CI 79.3-98.9%), specificity of 100% (CI 78.5-100.0%), positive predictive value (PPV) of 100%, negative predictive value (NPV) of 87.5%, and an overall accuracy of 95.6%. In contrast, the diagnostic performance of each individual miRNA used in the triple marker combination ranged from 53.3 to 80.0% in accuracy. While we acknowledge the need for further extensive studies involving larger patient cohorts and the consideration of additional miRNA candidates, our research undeniably highlights the potential of combining multiple markers as a robust methodology for identifying biomarkers among heterogeneous patient profiles.

Angiogenesis plays a crucial role in the growth of colorectal cancer (CRC). Recent studies have identified extracellular vesicles (EVs) in the tumor microenvironment as important mediators of cell-to-cell communication. However, the specific role and mechanisms of CRC-derived EVs in regulating tumor angiogenesis remain to be further investigated.

EVs were isolated from the conditioned medium of the CRC cells using ultracentrifugation. We investigated the effects of HT-29-derived EVs on tumor growth and angiogenesis in a subcutaneous HT-29 CRC tumor model in mice. Additionally, we evaluated the impact of HT-29-derived EVs on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Subsequently, bioinformatics analysis was performed to identify relevant signaling pathways, and pathway inhibitors were used to block the activation of these pathways, aiming to elucidate their roles in angiogenesis.

We found that HT-29-derived EVs can promote tumor growth and angiogenesis in vivo, as well as significantly enhance the proliferation, migration, and tube formation of HUVECs. Bioinformatics analysis revealed that HT-29-derived EVs may regulate angiogenesis through the JAK/STAT3 signaling pathway. Specifically, we observed that CRC-derived EVs promoted the phosphorylation of STAT3 (p-STAT3) and the expression of VEGFA in the nucleus of HUVECs. Treatment with the STAT3 inhibitor Stattic reduced the nuclear expression of p-STAT3, which impaired its function as a transcription factor, thereby inhibiting VEGFA expression and the pro-angiogenic effects of CRC-derived EVs.

EVs derived from CRC cells promote CRC tumor angiogenesis by regulating VEGFA through the JAK/STAT3 pathway in endothelial cells.

Colorectal cancer (CRC) remains the second most common cause of cancer-related mortality worldwide, necessitating advancements in early detection and innovative treatment strategies. MicroRNAs (miRNAs), small non-coding RNAs involved in gene regulation, have emerged as crucial players in the pathogenesis of CRC. This review synthesizes the latest findings on miRNA deregulated in precancerous lesions and in CRC. By examining the deregulation patterns of miRNAs across different stages of CRC development, this review highlights their potential as diagnostic tools. We specifically analyse the roles and diagnostic relevance of four miRNAs-miR-15b, miR-21, miR-31, and miR-146a-that consistently exhibit altered expression in CRC. The current knowledge of their role in key oncogenic pathways, drug resistance, and clinical relevance is discussed. Despite challenges posed by the heterogeneity of the research findings on miRNA deregulation and their role in CRC, integrating miRNA diagnostics into current screening methods holds promise for enhancing personalized medicine approaches. This review emphasizes the transformative potential of miRNAs in CRC diagnosis, paving the way for improved patient outcomes and novel therapeutic paradigms.

Exosomal microRNAs (exomiRs), transported via exosomes, play a pivotal role in intercellular communication. In cancer, exomiRs influence tumor progression by regulating key cellular processes such as proliferation, angiogenesis, and metastasis. Their role in mediating communication between cancer cells and the tumor microenvironment highlights their significance as potential diagnostic and therapeutic targets.

In this study, we aimed to characterize the role of exomiRs in influencing the pre-metastatic niche (PMN). Across 7 tumor types, including 4 cell lines and three tumors, we extracted high confidence exomiRs (Log FC >= 2 in exosomes relative to control) and their targets (experimentally identified and targeted by at least 2 exomiRs). Subsequently, we identified enriched pathways and selected the top 100 high-confidence exomiR targets based on the frequency of their appearance in the enriched pathways. These top 100 targets were consistently used throughout the analysis.

Cancer cell line and tumor derived ExomiRs have significantly higher GC content relative to genomic background. Pathway enriched among the top exomiR targets included general cancer-associated processes such as "wound healing" and "regulation of epithelial cell proliferation", as well as cancer-specific processes, such as "regulation of angiogenesis in kidney" (KIRC), "ossification" in lung (LUAD), and "positive regulation of cytokine production" in pancreatic cancer (PAAD). Similarly, 'Pathways in cancer' and 'MicroRNAs in cancer' ranked among the top 10 enriched KEGG pathways in all cancer types. ExomiR targets were not only enriched for cancer-specific tumor suppressor genes (TSG) but are also downregulated in pre-metastatic niche formed in lungs compared to normal lung. Motif analysis shows high similarity among motifs identified from exomiRs across cancer types. Our analysis recapitulates exomiRs associated with M2 macrophage differentiation and chemoresistance such as miR-21 and miR-222-3p, regulating signaling pathways such as PTEN/PI3/Akt, NF-κB, etc. Cox regression indicated that exomiR targets are significantly associated with overall survival of patients in TCGA. Lastly, a Support Vector Machine (SVM) model using exomiR target gene expression classified responders and non-responders to neoadjuvant chemotherapy with an AUROC of 0.96 (in LUAD), higher than other previously reported gene signatures.

Our study characterizes the pivotal role of exomiRs in shaping the PMN in diverse cancers, underscoring their diagnostic and therapeutic potential.

Liquid biopsy has emerged as a promising noninvasive approach for colorectal cancer (CRC) management. This review focuses on technologies detecting circulating nucleic acids, specifically circulating tumor DNA (ctDNA) and circulating RNA (cfRNA), as CRC biomarkers. Recent advancements in molecular technologies have enabled sensitive and specific detection of tumor-derived genetic material in bodily fluids. These include quantitative real-time PCR, digital PCR, next-generation sequencing (NGS), and emerging nanotechnology-based methods. For ctDNA analysis, techniques such as BEAMing and droplet digital PCR offer high sensitivity in detecting rare mutant alleles, while NGS approaches provide comprehensive genomic profiling. cfRNA detection primarily utilizes qRT-PCR arrays, microarray platforms, and RNA sequencing for profiling circulating microRNAs and discovering novel RNA biomarkers. These technologies show potential in early CRC detection, treatment response monitoring, minimal residual disease assessment, and tumor evolution tracking. However, challenges remain in standardizing procedures, optimizing detection limits, and establishing clinical utility across disease stages. This review summarizes current circulating nucleic acid detection technologies, their CRC applications, and discusses future directions for clinical implementation.

Exosomes play a key role in colorectal cancer (CRC) related processes. This review explores the various functions of exosomes in CRC and their potential as diagnostic markers, therapeutic targets, and drug delivery vehicles. Exosomal long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) significantly influence CRC progression. Specific exosomal lncRNAs are linked to drug resistance and tumor growth, respectively, highlighting their therapeutic potential. Similarly, miRNAs like miR-21, miR-10b, and miR-92a-3p, carried by exosomes, contribute to chemotherapy resistance by altering signaling pathways and gene expression in CRC cells. The review also discusses exosomes' utility in CRC diagnosis. Exosomes from cancer cells have distinct molecular signatures compared to healthy cells, making them reliable biomarkers. Specific exosomal lncRNAs (e.g., CRNDE-h) and miRNAs (e.g., miR-17-92a) have shown effectiveness in early CRC detection and monitoring of treatment responses. Furthermore, exosomes show promise as vehicles for targeted drug delivery. The potential of mesenchymal stem cell (MSC)-derived exosomes in CRC treatment is also noted, with their role varying from promoting to inhibiting tumor progression. The application of multi-omics approaches to exosome research is highlighted, emphasizing the potential for discovering novel CRC biomarkers through comprehensive genomic, transcriptomic, proteomic, and metabolomic analyses. The review also explores the emerging field of exosome-based vaccines, which utilize exosomes' natural properties to elicit strong immune responses. In conclusion, exosomes represent a promising frontier in CRC research, offering new avenues for diagnosis, treatment, and prevention. Their unique properties and versatile functions underscore the need for continued investigation into their clinical applications and underlying mechanisms.

This review comprehensively explores the complex interplay between extracellular vesicles (ECVs)/exosomes and circadian rhythms, with a focus on the role of this interaction in hepatocellular carcinoma (HCC). Exosomes are nanovesicles derived from cells that facilitate intercellular communication by transporting bioactive molecules such as proteins, lipids, and RNA/DNA species. ECVs are implicated in a range of diseases, where they play crucial roles in signaling between cells and their surrounding environment. In the setting of cancer, ECVs are known to influence cancer initiation and progression. The scope of this review extends to all cancer types, synthesizing existing knowledge on the various roles of ECVs. A unique aspect of this review is the emphasis on the circadian-controlled release and composition of exosomes, highlighting their potential as biomarkers for early cancer detection and monitoring metastasis. We also discuss how circadian rhythms affect multiple cancer-related pathways, proposing that disruptions in the circadian clock can alter tumor development and treatment response. Additionally, this review delves into the influence of circadian clock components on ECV biogenesis and their impact on reshaping the tumor microenvironment, a key component driving HCC progression. Finally, we address the potential clinical applications of ECVs, particularly their use as diagnostic tools and drug delivery vehicles, while considering the challenges associated with clinical implementation.

Globally, an increasing prevalence of colorectal cancer (CRC) prompts a need for the development of new methods for early tumor detection. MicroRNAs (also referred to as miRNAs) are short non-coding RNA molecules that play a pivotal role in the regulation of gene expression. MiRNAs are effectively transferred to extracellular vesicle (EVs) membrane sacs commonly released by cells. Our study aimed to examine the expression of miRNAs in four CRC cell lines and EVs derived from them (tumor EVs) in comparison to the normal colon epithelium cell line and its EVs. EVs were isolated by ultracentrifugation from the culture supernatant of SW480, SW620, SW1116, HCT116 and normal CCD841CoN cell lines and characterized according to the MISEV2023 guidelines. MiRNAs were analyzed by small RNA sequencing and validated by quantitative PCR. The performed analysis revealed 22 common miRNAs highly expressed in CRC cell lines and effectively transferred to tumor EVs, including miR-9-5p, miR-182-5p, miR-196b-5p, miR-200b-5p, miR-200c-3p, miR-425-5p and miR-429, which are associated with development, proliferation, invasion and migration of colorectal cancer cells, as well as in vesicle maturation and transport-associated pathways. In parallel, normal cells expressed miRNAs, such as miR-369 and miR-143, which play a role in proinflammatory response and tumor suppression. The analysis of selected miRNAs in plasma-derived EVs and tumor samples from CRC patients showed the similarity of miRNA expression profile between the patients' samples and CRC cell lines. Moreover, miR-182-5p, miR-196-5p, miR-425-5p and miR-429 were detected in several EV samples isolated from patients' plasma. Our results suggest that miR-182-5p, miR-196b-5p and miR-429 are differentially expressed between EVs from CRC patients and healthy donors, which might have clinical implications.

Early cancer detection and accurate monitoring are crucial to ensure increased patient survival. Recent research has focused on developing non-invasive biomarkers to diagnose cancer early and monitor disease progression at low cost and risk. Extracellular vesicles (EVs), nanosized particles secreted into extracellular spaces by most cell types, are gaining immense popularity as novel biomarker candidates for liquid cancer biopsy, as they can transport bioactive cargo to distant sites and facilitate intercellular communications. A literature search was conducted to discuss the current approaches for EV isolation and the advances in using EV-associated proteins, miRNA, mRNA, DNA, and lipids as liquid biopsies. We discussed the advantages and challenges of using these vesicles in clinical applications. Moreover, recent advancements in machine learning as a novel tool for tumor marker discovery are also highlighted.

Despite numerous reports on the alterations of microRNA-1246 (miR-1246) expression level in digestive system cancers, its role in gastrointestinal cancers (GICs) remains unclear. This meta-analysis aimed to assess the diagnostic potential of circulating miR-1246 in GICs.

Meta-disc version 1.4 and Comprehensive Meta-Analysis (CMA) version 3.7 software were used to calculate pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), area under the curve (AUC), Q*index and summary receiver-operating characteristic (SROC). Subgroup analyses were conducted for cancer type, sample type and geographical region. Publication bias was assessed using Begg's and Egger's tests.

A total of 14 articles involving 18 studies and 1526 participants (972 cases and 554 controls) were included. The diagnostic accuracy of miRNA-1246 in GICs was as follows: pooled sensitivity: 0.81 (95% CI: 0.79 - 0.83), specificity: 0.74 (95% CI: 0.71 - 0.77), PLR: 3.315 (95% CI: 2.33 - 4.72), NLR: 0.221 (95% CI: 0.153 - 0.319), DOR: 16.87 (95% CI: 9.45 - 30.09), AUC: 0.891, and Q*-index: 0.807. No publication bias was found based on Begg's (p = 0.172) and Egger's (p = 0.113) tests.

Circulating miR-1246 shows promise as a non-invasive biomarker for early detection of GICs.

Despite the existence of numerous studies investigating the diagnostic potential of blood microRNAs for colorectal cancer, the microRNAs under consideration vary widely, and comparative analysis of their diagnostic value is lacking. Consequently, this systematic review aims to identify the most effective microRNA blood tumor markers to enhance clinical decision-making in colorectal cancer screening.

A comprehensive search of databases, including PubMed, Embase, Web of Science, Scopus, and Cochrane, was conducted to identify case‒control or cohort studies that examined the diagnostic value of peripheral blood microRNAs in colorectal cancer. Studies were included if they provided sensitivity and specificity data, were published in English and were available between January 1, 2000, and February 10, 2023. The Critical Appraisal Skills Programme (CASP) checklist was employed for quality assessment. A Bayesian network meta-analysis was performed to estimate combined risk ratios (RRs) and 95% confidence intervals (CIs), with results presented via rankograms. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202,380,092.

From an initial pool of 2254 records, 79 met the inclusion criteria, encompassing a total of 90 microRNAs. The seven most frequently studied microRNAs (43 records) were selected for inclusion, all of which demonstrated moderate to high quality. miR-23, miR-92, and miR-21 exhibited the highest sensitivity and accuracy, outperforming traditional tumor markers CA19-9 and CEA in terms of RR values and 95% CI for both sensitivity and accuracy. With the exception of miR-17, no significant difference was observed between each microRNA and CA19-9 and CEA in terms of specificity.

Among the most extensively researched blood microRNAs, miR-23, miR-92, and miR-21 demonstrated superior diagnostic value for colorectal cancer due to their exceptional sensitivity and accuracy. This systematic review and network meta-analysis may serve as a valuable reference for the clinical selection of microRNAs as tumor biomarkers.

Circular RNAs (circRNAs) hold potential as diagnostic markers for colorectal cancer (CRC); however, their functional mechanisms remain incompletely elucidated. This work investigates the clinical implications of a unique set comprising six circRNAs derived from serum in CRC. Furthermore, we delve into the role of exosomal circ_0084043, originating from colorectal cancer-associated fibroblasts (CAFs), with a specific focus on its contribution to endothelial cell angiogenesis.

The study analyzed circRNA levels in serum samples obtained from both CRC and control groups using qRT-PCR. Additionally, exosomes originating from colorectal CAFs and normal fibroblasts (NFs) were purified and confirmed by electron microscopy and Western blotting techniques. The proangiogenic effects of CAF-derived exosomal circ_0084043 were assessed in endothelial cells through proliferation, migration, and in vitro capillary tube formation assays. Gain- and loss-of-function experiments were employed to clarify the role of the circ_0084043/miR-140-3p/HIF-1α axis in endothelial cell angiogenesis, utilizing luciferase reporter assay, Western blotting, and ELISA for mechanism elucidation.

The candidate circRNAs (circ_0060745, circ_001569, circ_007142, circ_0084043, Circ_BANP, and CiRS-7) exhibited notably elevated expression in CRC patient sera compared to the levels observed in healthy individuals. Except for CiRS-7, all circRNAs showed elevated expression in CRC patients with positive lymph node metastasis and advanced tumor stages. Exosomes released by colorectal CAFs augmented endothelial cell proliferation, migration, and angiogenesis by upregulating VEGF expression and secretion. Circ_0084043 was highly detected in endothelial cells treated with CAF-derived exosomes. Silencing circ_0084043 reduced VEGFA expression and diminished CAF exosome-induced endothelial cell processes, indicating its pivotal role in angiogenesis. Circ_0084043 sponges miR-140-3p, regulating HIF-1α, and a reverse relationship was also identified between miR-140-3p and VEGFA in endothelial cells. Inhibiting miR-140-3p mitigated circ_0084043 knockdown effects in CAF exosome-treated endothelial cells. Co-transfection of si-circ_0084043 and a miR-140-3p inhibitor reversed the inhibited migration and angiogenesis caused by circ_0084043 knockdown in CAF exosome-treated endothelial cells. Inhibiting miR-140-3p rescued reduced VEGFA expression due to circ_0084043 knockdown in endothelial cells exposed to CAF-derived exosomes, indicating modulation of the circ_0084043/miR-140-3p/VEGF signaling in CAF-derived exosome-induced angiogenesis.

This study unveiled a distinctive signature of six serum-derived circular RNAs, indicating their potential as promising diagnostic biomarkers for CRC. Importantly, exosomal circ_0084043 originating from colorectal CAFs was identified as playing a crucial role in endothelial cell angiogenesis, exerting its influence through the modulation of the miR-140-3p/HIF-1α/VEGF signaling axis.

Infection post-hematopoietic stem cell transplantation (HSCT) is one of the main causes of patient mortality. Fever is the most crucial clinical symptom indicating infection. However, current microbial detection methods are limited. Therefore, timely diagnosis of infectious fever and administration of antimicrobial drugs can effectively reduce patient mortality. In this study, serum samples were collected from 181 patients with HSCT with or without infection, as well as the clinical information. And more than 80 infectious-related microRNAs in the serum were selected according to the bulk RNA-seq result and detected in the 345 time-pointed serum samples by Q-PCR. Unsupervised clustering result indicates a close association between these microRNAs expression and infection occurrence. Compared to the uninfected cohort, more than 10 serum microRNAs were identified as the combined diagnostic markers in one formula constructed by the Random Forest (RF) algorithms, with a diagnostic accuracy more than 0.90. Furthermore, correlations of serum microRNAs to immune cells, inflammatory factors, pathgens, infection tissue, and prognosis were analyzed in the infection cohort. Overall, this study demonstrates that the combination of serum microRNAs detection and machine learning algorithms holds promising potential in diagnosing infectious fever after HSCT.

We provided an overview which evaluated the diagnostic performance of circulation EV biomarkers for CRC from PubMed, Medline, and Web of Science until 21 August 2022.Weidentified 48 studies that involved 7727 participants and evaluated 162 plasma/serum individual EV biomarkers including 117 RNAs and 45 proteins, as well as 45 EV biomarker panels for CRC detection. 12 studies evaluated the diagnostic performance of EV biomarkers for early CRC. The summarized sensitivity, specificity, and AUC value of individual EV RNAs and EV RNA panels were 76%, 75%, 0.87 and 82%, 79% and 0.90, respectively. Meanwhile, those of individual EV proteins and EV protein panels were 85%, 84%, 0.92 and 87%, 83%, 0.92, respectively. These results indicated that EV biomarker panels revealed superior diagnostic performance than the corresponding individual biomarkers. In early CRC, EV biomarkers showed available diagnostic value with the sensitivity, specificity, and AUC value of 80%, 75%, and 0.89.In subgroup analyses, EV miRNAs and LncRNAs held similar diagnostic value with the sensitivity, specificity and AUC value of 75%, 78%, 0.90 and 79%, 72%, 0.83, which was highly consistent with the whole EV RNAs. Significantly, the diagnostic values of EV miRNAs in plasma were marginally higher than those based on serum. In detail, the sensitivity, specificity, and AUC values were 79%, 81%, and 0.92 in plasma, as well as 74%, 77%, and 0.88 in serum, respectively. Therefore, circulation EV biomarkers could be considered as a promising biomarker for the early detection of CRC.

Extracellular vesicles (EVs) are lipid bilayer structures released by all cells and widely distributed in all biological fluids. EVs are implicated in diverse physiopathological processes by orchestrating cell-cell communication. Colorectal cancer (CRC) is one of the most common cancers worldwide, with metastasis being the leading cause of mortality in CRC patients. EVs contribute significantly to the advancement and spread of CRC by transferring their cargo, which includes lipids, proteins, RNAs, and DNAs, to neighboring or distant cells. Besides, they can serve as non-invasive diagnostic and prognostic biomarkers for early detection of CRC or be harnessed as effective carriers for delivering therapeutic agents. Autophagy is an essential cellular process that serves to remove damaged proteins and organelles by lysosomal degradation to maintain cellular homeostasis. Autophagy and EV release are coordinately activated in tumor cells and share common factors and regulatory mechanisms. Although the significance of autophagy and EVs in cancer is well established, the exact mechanism of their interplay in tumor development is obscure. This review focuses on examining the specific functions of EVs in various aspects of CRC, including progression, metastasis, immune regulation, and therapy resistance. Further, we overview emerging discoveries relevant to autophagy and EVs crosstalk in CRC.

Gastrointestinal (GI) cancers account for one-fourth of the global cancer incidence and are incriminated to cause one-third of cancer-related deaths. GI cancer includes esophageal, gastric, liver, pancreatic, and colorectal cancers, mostly diagnosed at advanced stages due to a lack of accurate markers for early stages. The invasiveness of diagnostic methods like colonoscopy for solid biopsy reduces patient compliance as it cannot be frequently used to screen patients. Therefore, minimally invasive approaches like liquid biopsy may be explored for screening and early identification of gastrointestinal cancers. Liquid biopsy involves the qualitative and quantitative determination of certain cancer-specific biomarkers in body fluids such as blood, serum, saliva, and urine to predict disease progression, therapeutic tolerance, toxicities, and recurrence by evaluating minimal residual disease and its correlation with other clinical features. In this review, we deliberate upon various tumor-specific cellular and molecular entities such as circulating tumor cells (CTCs), tumor-educated platelets (TEPs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), exosomes, and exosome-derived biomolecules and cite recent advances pertaining to their use in predicting disease progression, therapy response, or risk of relapse. We also discuss the technical challenges associated with translating liquid biopsy into clinical settings for various clinical applications in gastrointestinal cancers.

Rhabdomyosarcoma is a pediatric cancer associated with aggressiveness and a tendency to develop metastases. Fusion-negative rhabdomyosarcoma (FN-RMS) is the most commonly occurring subtype of RMS, where metastatic disease can hinder treatment success and decrease survival rates. RMS-derived exosomes were previously demonstrated to be enriched with miRNAs, including miR-1246, possibly contributing to disease aggressiveness. We aimed to decipher the functional impact of exosomal miR-1246 on recipient cells and its role in promoting aggressiveness. Treatment of normal fibroblasts with FN-RMS-derived exosomes resulted in a significant uptake of miR-1246 paired with an increase in cell proliferation, migration, and invasion. In turn, delivery of miR-1246-mimic lipoplexes promoted fibroblast proliferation, migration, and invasion in a similar manner. Conversely, when silencing miR-1246 in FN-RMS cells, the resulting derived exosomes demonstrated reversed effects on recipient cells' phenotype. Delivery of exosomal miR-1246 targets GSK3β and promotes β-catenin nuclear accumulation, suggesting a deregulation of the Wnt pathway, known to be important in tumor progression. Finally, a pilot clinical study highlighted, for the first time, the presence of high exosomal miR-1246 levels in RMS patients' sera. Altogether, our results demonstrate that exosomal miR-1246 has the potential to alter the tumor microenvironment of FN-RMS cells, suggesting its potential role in promoting oncogenesis.

Colorectal cancer (CRC) is the third most common cancer affecting people. The discovery of new, non-invasive, specific, and sensitive molecular biomarkers for CRC may assist in the diagnosis and support therapeutic decision making. Exosomal miRNAs have been demonstrated in carcinogenesis and CRC development, which makes these miRNAs strong biomarkers for CRC. Deep sequencing allows a robust high-throughput informatics investigation of the types and abundance of exosomal miRNAs. Thus, exosomal miRNAs can be efficiently examined as diagnostic biomarkers for disease screening. In the present study, a number of 660 mature miRNAs were detected in patients diagnosed with CRC at different stages. Of which, 29 miRNAs were differentially expressed in CRC patients compared with healthy controls. Twenty-nine miRNAs with high abundance levels were further selected for subsequent analysis. These miRNAs were either highly up-regulated (e.g., let-7a-5p, let-7c-5p, let-7f-5p, let-7d-3p, miR-423-5p, miR-3184-5p, and miR-584) or down-regulated (e.g., miR-30a-5p, miR-99-5p, miR-150-5p, miR-26-5p and miR-204-5p). These miRNAs influence critical genes in CRC, leading to either tumor growth or suppression. Most of the reported diagnostic exosomal miRNAs were shown to be circulating in blood serum. The latter is a novel miRNA that was found in exosomal profile of blood serum. Some of the predicted target genes of highly expressed miRNAs participate in several cancer pathways, including CRC pathway. These target genes include tumor suppressor genes, oncogenes and DNA repair genes. Main focus was given to multiple critical signaling cross-talking pathways including transforming growth factor β (TGFβ) signaling pathways that are directly linked to CRC. In conclusion, we recommend further analysis in order to experimentally confirm exact relationships between selected differentially expressed miRNAs and their predicted target genes and downstream functional consequences.

Alcohol consumption may impact and shape brain development through perturbed biological pathways and impaired molecular functions. We investigated the relationship between alcohol consumption rates and neuron-enriched extracellular vesicles' (EVs') microRNA (miRNA) expression to better understand the impact of alcohol use on early life brain biology. Neuron-enriched EVs' miRNA expression was measured from plasma samples collected from young people using a commercially available microarray platform while alcohol consumption was measured using the Alcohol Use Disorders Identification Test. Linear regression and network analyses were used to identify significantly differentially expressed miRNAs and to characterize the implicated biological pathways, respectively. Compared to alcohol naïve controls, young people reporting high alcohol consumption exhibited significantly higher expression of three neuron-enriched EVs' miRNAs including miR-30a-5p, miR-194-5p, and miR-339-3p, although only miR-30a-5p and miR-194-5p survived multiple test correction. The miRNA-miRNA interaction network inferred by a network inference algorithm did not detect any differentially expressed miRNAs with a high cutoff on edge scores. However, when the cutoff of the algorithm was reduced, five miRNAs were identified as interacting with miR-194-5p and miR-30a-5p. These seven miRNAs were associated with 25 biological functions; miR-194-5p was the most highly connected node and was highly correlated with the other miRNAs in this cluster. Our observed association between neuron-enriched EVs' miRNAs and alcohol consumption concurs with results from experimental animal models of alcohol use and suggests that high rates of alcohol consumption during the adolescent/young adult years may impact brain functioning and development by modulating miRNA expression.

Colorectal cancer (CRC) ranks third in cancer incidence and stands as the second leading cause of cancer-related deaths globally. CRC tumorigenesis results from a cumulative set of genetic and epigenetic alterations, disrupting cancer-regulatory processes like cell proliferation, metabolism, angiogenesis, cell death, invasion, and metastasis. Key epigenetic modifications observed in cancers encompass abnormal DNA methylation, atypical histone modifications, and irregularities in noncoding RNAs, such as microRNAs and long noncoding RNAs. The advancement in genomic technologies has positioned these genetic and epigenetic shifts as potential clinical biomarkers for CRC patients. This review concisely covers the fundamental principles of CRC-associated epigenetic changes, and examines in detail their emerging role as biomarkers for early detection, prognosis, and treatment response prediction.

Tumor-associated macrophages (TAMs) play a crucial role in promoting tumor growth and dissemination, motivating a search for key targets to interfere with the activation of TAMs or reprogram TAMs into the tumor-suppressive type. To gain insight into the mechanisms of macrophage polarization, a designed co-culture system is established, allowing for the education of macrophages in a manner that closely mimics the intricacies of TAMs in the tumor immune microenvironment (TIME). Through database mining, exosomal miR-1246 is identified and is then validated. Exosomal miR-1246-driven polarization of TAMs disrupts the infiltration and function of CD8+ T cells. Mechanically, the amassment of exosomal miR-1246 stems from TUT7-mediated degradation of small noncoding RNA, a process stabilized by SNRPB, but not the precursor of miR-1246. Moreover, an Exo-motif is present in the exosomal miR-1246 sequence, enabling it to bind with the exosomal sorting protein hnRNPA2B1. RNA-seq analysis reveals that exogenous miR-1246 modulates the polarization of TAMs at a post-transcriptional level, emphasizing the pivotal role of the NLRP3 in macrophage polarization. In conclusion, the findings underscore the importance of exosomal miR-1246 as a trigger of macrophage reprogramming and uncover a novel mechanism for its enhanced presence in the TIME.

MicroRNA as potential biomarker for early diagnosis, differentiating various stages, interpreting the success of postoperative curative surgery and predicting early relapse of Colorectal cancer.In the realm of medical research, the quest to find effective biomarkers for various diseases has always been a top priority. Colorectal cancer (CRC), one of the leading causes of cancer-related deaths worldwide, is no exception. The emergence of microRNA (mRNA) as a potential biomarker for CRC has sparked immense interest among scientists and clinicians alike. mRNA, a molecule responsible for translating genetic information into functional proteins, presents a promising avenue for early detection and personalized treatment of this deadly disease. By analyzing the specific patterns and levels of mRNA expression in CRC cells, researchers have the ability to identify signatures that can aid in accurate diagnosis, predict patient prognosis, and even guide targeted therapies. This breakthrough in molecular biology not only enhances our understanding of CRC but also holds the potential to revolutionize the field of cancer diagnostics and treatment. In this article, we will delve deeper into the potential of mRNA as a biomarker for CRC, exploring its benefits and challenges in the field of cancer research.

Exosomes, which are tiny particles released by cells, have the ability to transport various molecules, including proteins, lipids, and genetic material containing non-coding RNAs (ncRNAs). They are associated with processes like cancer metastasis, immunity, and tissue repair. Clinical trials have shown exosomes to be effective in treating cancer, inflammation, and chronic diseases. Mesenchymal stem cells (MSCs) and dendritic cells (DCs) are common sources of exosome production. Exosomes have therapeutic potential due to their ability to deliver cargo, modulate the immune system, and promote tissue regeneration. Bioengineered exosomes could revolutionize disease treatment. However, more research is needed to understand exosomes in tumor growth and develop new therapies. This paper provides an overview of exosome research, focusing on cancer and exosome-based therapies including chemotherapy, radiotherapy, and vaccines. It explores exosomes as a drug delivery system for cancer therapy, highlighting their advantages. The article discusses using exosomes for various therapeutic agents, including drugs, antigens, and RNAs. It also examines challenges with engineered exosomes. Analyzing exosomes for clinical purposes faces limitations in sensitivity, specificity, and purification. On the other hand, Nanotechnology offers solutions to overcome these challenges and unlock exosome potential in healthcare. Overall, the article emphasizes the potential of exosomes for personalized and targeted cancer therapy, while acknowledging the need for further research.