Exosome Biology Research Articles

The role and clinical applications of exosomes in cancer drug resistance

Tumor-secreted exosomes are heterogeneous multi-signal messengers that support cancer growth and dissemination by mediating intercellular crosstalk and activating signaling pathways. Distinct from previous reviews, we focus intently on exosome-therapeutic resistance dynamics and summarize the new findings about the regulation of cancer treatment resistance by exosomes, shedding light on the complex processes via which these nanovesicles facilitate therapeutic refractoriness across various malignancies. Future research in exosome biology can potentially transform diagnostic paradigms and therapeutic interventions for cancer management. This review synthesizes recent insights into the exosome-driven regulation of cancer drug resistance, illuminates the sophisticated mechanisms by which these nanovesicles facilitate therapeutic refractoriness across various malignancies, and summarizes some strategies to overcome drug resistance.

Emerging understandings of the role of exosomes in atherosclerosis.

Atherosclerosis remains a major contributor to cardiovascular disease, the leading cause of global morbidity and mortality. Despite the elucidation of several molecular, biochemical, and cellular aspects that contribute to the etio-pathogenesis of atherosclerosis, much remains to be understood about the onset and progression of this disease. Emerging evidence supports a role for exosomes in the cellular basis of atherosclerosis. Indeed, exosomes of activated monocytes seem to accentuate a positive feedback loop that promotes recruitment of pro-inflammatory leukocytes. Moreover, in addition to their role in promoting proliferation and invasion of vascular smooth muscle cells, exosomes can also induce neovascularization within lesions and increase endothelial permeability, two important features of fibrous plaques. Depending on their sources and cargo, exosomes can also induce clot formation and contribute to other hallmarks of atherosclerosis. Taken together, it is becoming increasingly evident that a better understanding of exosome biology is integral to elucidating the pathogenesis of atherosclerosis, and may thus provide insight into a potentially new therapeutic target for this disease.

Research progress of exosomes from different sources in myocardial ischemia.

Ischemic heart disease refers to the imbalance between the supply and demand of myocardial blood; it has various causes and results in a class of clinical diseases characterized by myocardial ischemia (MI). In recent years, the incidence of cardiovascular disease has become higher and higher, and the number of patients with ischemic heart disease has also increased year by year. Traditional treatment methods include drug therapy and surgical treatment, both of which have limitations. The former maybe develop risks of drug resistance and has more significant side effects, while the latter may damage blood vessels and risk infection. At this stage, a new cell-free treatment method needs to be explored. Many research results have shown that exosomes from different cell sources can protect the ischemic myocardium via intercellular action methods, such as promoting angiogenesis, inhibiting myocardial fibrosis, apoptosis and pyroptosis, and providing a new basis for the treatment of MI. In this review, we briefly introduce the formation and consequences of myocardial ischemia and the biology of exosomes, and then focus on the role and mechanism of exosomes from different sources in MI. We also discuss the role and mechanism of exosomes pretreated with Chinese and Western medicines on myocardial ischemia. We also discuss the potential of exosomes as diagnostic markers and therapeutic drug for MI.

Research progress on exosomes and their non-coding RNAs in the diagnosis of neurodegenerative diseases

Neurodegenerative diseases, originating from irreversible progressive loss of neuronal structure or function, are difficult to diagnose and treat. They vary widely in scope and have poor prevention and prognosis. Therefore, research on their early diagnosis is particularly important. Exosomes are small vesicles of cellular origin that contain various bioactive small molecules, such as proteins, RNAs, and DNAs, and play important roles in intercellular communication. Recent studies have shown that exosomes and their non-coding RNAs are key factors in the pathogenesis of various neurodegenerative diseases. Therefore, exosomes and their non-coding RNAs may provide a breakthrough for the early diagnosis of neurodegenerative diseases. This review summarizes the biology of exosomes and the current research progress of exosomes and their non-coding RNAs in diagnosing neurodegenerative diseases and further explores the challenges and prospects they face.

Review article: An overview of exosomes in biology and their potential applications in regenerative medicine

Extracellular vesicles (EVs), commonly acknowledged as Exosomes, are tiny, single-membrane, secreted organelles that range in size from 40 to 150 nm. They are noticeably abundant in various proteins, lipids, nucleic acids, and glycoconjugates and share the same structure as cells. Numerous and non-hematopoietic cell types continuously manufacture and release stable, less toxic, and biocompatible exosomes with many complex compounds (in the form of various signaling molecules, miRNA, and mRNA) in the liquid parts of the body. Exosomes help in intercellular communication/transfer of proteins, RNA, cell differentiation, immune signaling, delivering antigens, angiogenesis, and stress response. In recent studies, researchers found that Mesenchymal Stem cells (MSCs) generate exosomes that symbolize biological processes like tissue regeneration by encasing and delivering active biomolecular species to the infected/damaged cells and tissues. The most extensive research in regenerative medicine has focused on MSCs-Exosomes. Regenerative medicine plays a crucial role in restoring the damaged/lost parts of organs and tissues and aiding in wound healing. Immunomodulation and tissue repair are possible by introducing Mesenchymal Stem cell (MSC) exosomes, which have triggered remodeling reactions. They produce local anti-inflammatory and healing signals crucial for regeneration and tissue repair. The primary goal of this review is to highlight the MSCs-exosome’s mechanism of action and its therapeutic uses in clinical settings. Also, it highlights new developments in employing MSCsexosomes to treat various ailments and disorders.

Exosome- Machine Learning Integration in Biomedicine: Advancing Diagnosis and Biomarker Discovery.

Exosomes, small extracellular vesicles (sEVs) secreted by various cell types, play crucial roles in intercellular communication and are increasingly recognized as valuable biomarkers for disease diagnosis and therapeutic targets. Meanwhile, machine learning (ML) techniques have revolutionized biomedical research by enabling the analysis of complex datasets and highly accurate prediction of disease outcomes. Exosomes, with their diverse cargo of proteins, nucleic acids, and lipids, offer a rich source of molecular information reflecting the physiological state of cells. Integrating exosome analysis with ML algorithms, including supervised and unsupervised learning techniques, allows for identifying disease-specific biomarkers and predicting disease outcomes based on exosome profiles. Integrating exosome biology with ML presents a promising avenue for advancing biomedical research and clinical practice. This review explores the intersection of exosome biology and ML in biomedicine, highlighting the importance of integrating these disciplines to advance our understanding of disease mechanisms and biomarker discovery.

Clinical Applications of Exosomes: A Critical Review.

Exosomes, small membrane-bound vesicles secreted by cells, have gained significant attention for their therapeutic potential. Measuring 30-100 nm in diameter and derived from various cell types, exosomes play a crucial role in intercellular communication by transferring proteins, lipids, and RNA between cells. This review analyzes existing literature on the clinical applications of exosomes. We conducted a comprehensive search of peer-reviewed articles and clinical trial data to evaluate the benefits, limitations, and challenges of exosome-based therapies. Key areas of focus included regenerative medicine, cancer therapy, gene therapy, and diagnostic biomarkers. This review highlights the vast clinical applications of exosomes. In regenerative medicine, exosomes facilitate tissue repair and regeneration. In cancer therapy, exosomes can deliver therapeutic agents directly to tumor cells. In gene therapy, exosomes serve as vectors for gene delivery. As diagnostic biomarkers, they are useful in diagnosing various diseases. Challenges such as the isolation, purification, and characterization of exosomes were identified. Current clinical trials demonstrate the potential of exosome-based therapies, though they also reveal significant hurdles. Regulatory issues, including the need for standardization and validation of exosome products, are critical for advancing these therapies. While significant progress has been made in understanding exosome biology, further research is essential to fully unlock their clinical potential. Addressing challenges in isolation, purification, and regulatory standardization is crucial for their successful application in clinical practice. This review provides a concise overview of the clinical applications of exosomes, emphasizing both their therapeutic promise and the obstacles that need to be overcome.

Standardized Reporting of Research on Exosomes to Ensure Rigor and Reproducibility.

Significance: The study of extracellular vesicles (EVs), especially exosomes, has unlocked new avenues in understanding cellular communication and potential therapeutic applications. Recent Advances: Advancements in EV research have shown significant contributions from the International Society for Extracellular Vesicles (ISEV), in establishing methodological standards. The evolution of the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines from 2014 to 2023 reflects enhanced research rigor and reproducibility. The launch of EV-TRACK platform promotes uniformity and reproducibility by providing a centralized repository for data sharing and standardization practices. Furthermore, databases like EVpedia and ExoCarta have facilitated data sharing and collaboration within the scientific community. Concurrently, exosome-based therapies have emerged as a forefront area within regenerative medicine and targeted drug delivery, showcasing the potential of exosomes in promoting tissue regeneration. Critical Issues: Despite advancements, the field grapples with challenges such as vesicular heterogeneity, EV isolation complexity, and standardization. These issues impact research reproducibility and clinical applications. The inconsistency in exosomal preparations in clinical trials poses significant challenges to therapeutic efficacy and safety. Future Directions: The review outlines critical areas for future research, including the need for technological innovation in EV isolation and characterization, the establishment of standardized protocols, and a deeper understanding of exosome biology. The review also highlights the need to reassess guidelines, develop new EV isolation and characterization technologies, and establish standardized protocols to overcome current limitations. Emphasis is placed on interdisciplinary research and collaboration to address the complexities of EV biology, improve clinical trial design, and ultimately realize exosome's therapeutic and diagnostic potential. Continued evaluation and rigorous scientific validation are essential for successful exosome integration.

Exosomes in Osteoarthritis: A Review on Their Isolation Techniques and Therapeutic Potential.

Exosomes are the smallest extracellular vesicles (30-150nm) secreted by all cell types, including synovial fluid. However, because biological fluids are complex, heterogeneous, and contain contaminants, their isolation is difficult and time-consuming. Furthermore, the pathophysiology of osteoarthritis (OA)involves exosomescarryingcomplex components that cause macrophages to release chemokines and proinflammatory cytokines. This narrative review aims to provide in-depth insights into exosome biology, isolation techniques, role in OA pathophysiology, and potential role in future OA therapeutics. A literature search was conducted using PubMed, Scopus, and Web of Science databases for studies involving exosomes in the osteoarthritis using keywords "Exosomes" and "Osteoarthritis". Relevant articles in the last 15years involving both human and animal models were included. Studies involving exosomes in other inflammatory diseases were excluded. Despite some progress, conventional techniques for isolating exosomes remain laborious and difficult, requiring intricate and time-consuming procedures acrossvarious body fluids and sample origins. Moreover, exosomes are involved in various physiological processes associated with OA, like cartilage calcification, degradation of osteoarthritic joints, and inflammation. The process of achieving standardization, integration, and high throughput of exosome isolation equipment is challenging and time-consuming. The integration of various methodologies can be employed to effectively address specific issues by leveraging their complementary benefits. Exosomes have the potential to effectively repair damaged cartilage OA, reduce inflammation, and maintain abalance between the formation and breakdown of cartilage matrix, therefore showing promise as a therapeutic option for OA.

Exosomes in Atherosclerosis: Role in the Pathogenesis and Targets for Therapy.

Atherosclerotic cardiovascular disease (ASCVD) is an advanced chronic inflammatory disease and the leading cause of death worldwide. The pathological development of ASCVD begins with atherosclerosis, characterised by a pathological remodelling of the arterial wall, lipid accumulation and build-up of atheromatous plaque. As the disease advances, it narrows the vascular lumen and limits the blood, leading to ischaemic necrosis in coronary arteries. Exosomes are nano-sized lipid vesicles of different origins that can carry many bioactive molecules from their parental cells, thus playing an important role in intercellular communication. The roles of exosomes in atherosclerosis have recently been intensively studied, advancing our understanding of the underlying molecular mechanisms. In this review, we briefly introduce exosome biology and then focus on the roles of exosomes of different cellular origins in atherosclerosis development and progression, functional significance of their cargoes and physiological impact on recipient cells. Studies have demonstrated that exosomes originating from endothelial cells, vascular smooth muscle cells, macrophages, dendritic cells, platelets, stem cells, adipose tissue and other sources play an important role in the atherosclerosis development and progression by affecting cholesterol transport, inflammatory, apoptotic and other aspects of the recipient cells' metabolism. MicroRNAs are considered the most significant type of bioactive molecules transported by exosomes and involved in ASCVD development. Finally, we review the current achievements and limitations associated with the use of exosomes for the diagnosis and treatment of ASCVD.

Present and Future Use of Exosomes in Dermatology

Abstract Exposure to external environmental stimuli can lead to skin aging, pigmentation, hair loss, and various immune-mediated as well as connective tissue diseases. Although conventional treatments are routinely used and favoured, they fail to achieve an adequate balance between clinical and cosmetic outcomes. Exosomes are vesicles with a lipid bilayer released by several cell types. These bioactive vesicles play a crucial role in intercellular communication and in several other physiological and pathological processes. They serve as vehicles for bioactive substances including lipids, nucleic acids, and proteins, making them appealing as cell-free treatments. According to studies, exosomes play a vital role in preventing scarring, and senescence, and promoting wound healing. Moreover, research on the biology of exosomes is growing, which has enabled the creation of specific guidelines and quality control methodologies to support their potential implementation in the future. In this review, we have mainly focused on the role of exosomes in various dermatological diseases, their clinical applications, and the potential for further research pertaining to this.

A comprehensive database of exosome molecular biomarkers and disease-gene associations

Exosomes play a crucial role in intercellular communication and can be used as biomarkers for diagnostic and therapeutic clinical applications. However, systematic studies in cancer-associated exosomal nucleic acids remain a big challenge. Here, we developed ExMdb, a comprehensive database of exosomal nucleic acid biomarkers and disease-gene associations curated from published literature and high-throughput datasets. We performed a comprehensive curation of exosome properties including 4,586 experimentally supported gene-disease associations, 13,768 diagnostic and therapeutic biomarkers, and 312,049 nucleic acid subcellular locations. To characterize expression variation of exosomal molecules and identify causal factors of complex diseases, we have also collected 164 high-throughput datasets, including bulk and single-cell RNA sequencing (scRNA-seq) data. Based on these datasets, we performed various bioinformatics and statistical analyses to support our conclusions and advance our knowledge of exosome biology. Collectively, our dataset will serve as an essential resource for investigating the regulatory mechanisms of complex diseases and improving the development of diagnostic and therapeutic biomarkers.

A Plasma Exosomal Metabolic Profiling of Nonalcoholic Fatty Liver Disease Patients Complicated with Impaired Fasting Glucose.

Nonalcoholic fatty liver disease is considered as the hepatic manifestation of metabolic syndrome. Detection of circulating exosomes together with metabolomic analysis of their cargo would provide early signals for metabolic derangements and complications associated with nonalcoholic fatty liver disease. Therefore, this study profiled exosomal metabolome of patients with nonalcoholic fatty liver disease and impaired fasting glucose. Plasma exosomes were extracted from nonalcoholic fatty liver disease patients with or without impaired fasting glucose through differential ultracentrifugation. Their metabolite profiles were examined by ultrahigh-performance liquid chrom atography-quadrupole time-of-flight mass spectrometry. Pathway analysis was carried out on platform MetaboAnalyst 4.0. Thirty-nine patients were enrolled, including nonalcoholic fatty liver disease-alone group (n = 26) and age-and gender-comparable nonalcoholic fatty liver disease plus impaired fasting glucose group (n = 13). Although less than and different from their plasma counterparts, a total of 10 significantly differential exosomal metabolites were identified. Nonalcoholic fatty liver disease plus impaired fasting glucose group had higher concentrations of linoleic acid, palmitamide, stearamide, and oleamide, as well as a lower concentration of phosphatidylethanolamine [20:5(5Z,8Z,11Z,14Z,17Z)/20:5(5Z,8Z,11Z,14Z,17Z)]. Pathway analysis showed an obviously changed metabolism of linoleic acid. Metabolomic analysis of plasma exosomes revealed a distinct change in fatty acids and related pathways in nonalcoholic fatty liver disease patients with impaired fasting glucose. These preliminary results provide a metabolomic snapshot and basis for further investigation of exosome biology for these patients.

Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair.

Exosome therapy holds great promise as a novel approach to improve acute skin wound healing. This review provides a comprehensive overview of the current understanding of exosome biology and its potential applications in acute skin wound healing and beyond. Exosomes, small extracellular vesicles secreted by various stem cells, have emerged as potent mediators of intercellular communication and tissue repair. One advantage of exosome therapy is its ability to avoid potential risks associated with stem cell therapy, such as immune rejection or stem cells differentiating into unwanted cell types. However, further research is necessary to optimize exosome therapy, not only in the areas of exosome isolation, characterization, and engineering, but also in determining the optimal dose, timing, administration, and frequency of exosome therapy. Thus, optimization of exosome therapy is critical for the development of more effective and safer exosome-based therapies for acute skin wound healing and other diseases induced by cancer, ischemia, or inflammation. This review provides valuable insights into the potential of exosome therapy and highlights the need for further research to optimize exosome therapy for clinical use.

Translational studies of exosomes in sports medicine - a mini-review.

This review in sports medicine focuses on the critical role of exosomes in managing chronic conditions and enhancing athletic performance. Exosomes, small vesicles produced by various cells, are essential for cellular communication and transporting molecules like proteins and nucleic acids. Originating from the endoplasmic reticulum, they play a vital role in modulating inflammation and tissue repair. Their significance in sports medicine is increasingly recognized, particularly in healing athletic injuries, improving articular cartilage lesions, and osteoarthritic conditions by modulating cellular behavior and aiding tissue regeneration. Investigations also highlight their potential in boosting athletic performance, especially through myocytes-derived exosomes that may enhance adaptability to physical training. Emphasizing a multidisciplinary approach, this review underlines the need to thoroughly understand exosome biology, including their pathways and classifications, to fully exploit their therapeutic potential. It outlines future directions in sports medicine, focusing on personalized treatments, clinical evaluations, and embracing technological advancements. This research represents a frontier in using exosomes to improve athletes' health and performance capabilities.

Extracellular vesicles and their therapeutic applications: a review article (part 2).

Extracellular vesicles (EVs) have emerged as a fascinating area of research in molecular biology, with diverse therapeutic applications. These small membrane-bound structures, released by cells into the extracellular space, play a crucial role in intercellular communication and hold great potential for advancing medical treatments. The aim of this study is to have a narrative review on the use and therapeutic applications of EVs. Their unique characteristics, including stability, biocompatibility, and the ability to traverse biological barriers, make them promising tools for targeted drug delivery. By engineering EVs to encapsulate specific cargo molecules, such as therapeutic proteins, small interfering RNA (siRNA), or anti-cancer drugs, researchers can enhance drug stability and improve targeted delivery to desired cells or tissues. This approach can minimize off-target effects and improve therapeutic efficacy. Based on our literature search, we found that EVs can be used as biomarkers to predict diseases. Although much progress has been made in understanding the biology and function of exosomes, there are still unanswered questions that require further research. This includes identifying appropriate and safe techniques for producing exosomes in large quantities, determining which types of cells are suitable for exosome donor cells for therapeutic purposes, and investigating the safety of exosomes in human studies. Overall, the use of exosomes in clinical therapeutic applications requires a strong understanding of molecular signaling cascades and exosome profiles, as well as the specificity and sensitivity of biomarker and drug delivery methods.

Exosomes in liquid biopsy and oncology: Nanotechnological interplay and the quest to overcome cancer drug resistance

Exosomes, small extracellular vesicles of endocytic origin, have emerged as pivotal mediators in intercellular communication, driving transformative advancements across diverse fields of biology and medicine. This comprehensive review delves into the multifaceted roles of exosomes in health and disease, elucidating their biogenesis, cargo composition, and far-reaching implications. Exosomes, secreted by virtually all cell types, encapsulate a cargo comprising proteins, lipids, and nucleic acids, reflecting their cellular origin. Their molecular cargo modulates cellular processes, facilitating complex signalling cascades and contributing to the pathogenesis of various diseases, including cancer, neurodegenerative disorders, and infectious diseases. In cancer, exosomes serve as messengers of tumorigenesis and metastasis, orchestrating critical events within the tumor microenvironment. Furthermore, exosomes participate in drug resistance mechanisms, presenting significant challenges in cancer therapy. The diagnostic potential of exosomes, particularly in the context of liquid biopsy, is underscored by their presence in various biofluids. This offers non-invasive disease monitoring and biomarker discovery, revolutionizing early detection and monitoring strategies. Additionally, exosomes have gained recognition as therapeutic vehicles, holding promise for targeted drug delivery, immunomodulation, and regenerative medicine. This review comprehensively explores the ever-expanding landscape of exosome biology, emphasizing their roles in health and disease. It underscores the transformative potential of exosomes in liquid biopsy-based diagnostics and therapeutics while acknowledging the complexities and challenges that lie ahead in harnessing their full clinical utility.

A Plasma Exosomal Metabolic Profiling of Nonalcoholic Fatty Liver Disease Patients Complicated with Impaired Fasting Glucose.

Nonalcoholic fatty liver disease is considered as the hepatic manifestation of metabolic syndrome. Detection of circulating exosomes together with metabolomic analysis of their cargo would provide early signals for metabolic derangements and complications associated with nonalcoholic fatty liver disease. Therefore, this study profiled exosomal metabolome of patients with nonalcoholic fatty liver disease and impaired fasting glucose. Plasma exosomes were extracted from nonalcoholic fatty liver disease patients with or without impaired fasting glucose through differential ultracentrifugation. Their metabolite profiles were examined by ultrahigh-performance liquid chrom atography-quadrupole time-of-flight mass spectrometry. Pathway analysis was carried out on platform MetaboAnalyst 4.0. Thirty-nine patients were enrolled, including nonalcoholic fatty liver disease-alone group (n = 26) and age-and gender-comparable nonalcoholic fatty liver disease plus impaired fasting glucose group (n = 13). Although less than and different from their plasma counterparts, a total of 10 significantly differential exosomal metabolites were identified. Nonalcoholic fatty liver disease plus impaired fasting glucose group had higher concentrations of linoleic acid, palmitamide, stearamide, and oleamide, as well as a lower concentration of phosphatidylethanolamine [20:5(5Z,8Z,11Z,14Z,17Z)/20:5(5Z,8Z,11Z,14Z,17Z)]. Pathway analysis showed an obviously changed metabolism of linoleic acid. Metabolomic analysis of plasma exosomes revealed a distinct change in fatty acids and related pathways in nonalcoholic fatty liver disease patients with impaired fasting glucose. These preliminary results provide a metabolomic snapshot and basis for further investigation of exosome biology for these patients.

Exomap1 mouse: A transgenic model for in vivo studies of exosome biology

Exosomes are small extracellular vesicles (sEVs) of ∼30–150 nm in diameter that are enriched in exosome marker proteins and play important roles in health and disease. To address large unanswered questions regarding exosome biology in vivo, we created the Exomap1 transgenic mouse, which in response to Cre recombinase expresses the most highly enriched exosomal marker protein known, human CD81, fused to mNeonGreen (HsCD81mNG), and prior to Cre expresses a mitochondrial red fluorescent protein. Validation of the exomap1 mouse with eight distinct Cre drivers demonstrated that HsCD81mNG was expressed only in response to Cre, that murine cells correctly localized HsCD81mNG to the plasma membrane, and that this led to the secretion of HsCD81mNG in EVs that had the size (∼70–80 nm), topology, and composition of exosomes. Furthermore, cell type-specific activation of the exomap1 transgene allowed us to use quantitative single molecule localization microscopy to calculate the cell type-specific contribution to biofluid exosome populations. Specifically, we show that neurons contribute ∼1% to plasma and cerebrospinal fluid exosome populations whereas hepatocytes contribute ∼15% to plasma exosome populations, numbers that reflect the known vascular permeabilities of brain and liver. These observations validate the use of Exomap1 mouse models for in vivo studies of exosome biology.

Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities.

The development of therapy resistance still represents a major hurdle in treating cancers, leading to impaired treatment success and increased patient morbidity. The establishment of minimally invasive liquid biopsies is a promising approach to improving the early diagnosis, as well as therapy monitoring, of solid tumors. Because of their manifold functions in the tumor microenvironment, tumor-associated small extracellular vesicles, referred to as exosomes, have become a subject of intense research. Besides their important roles in cancer progression, metastasis, and the immune response, it has been proposed that exosomes also contribute to the acquisition and transfer of therapy resistance, mainly by delivering functional proteins and RNAs, as well as facilitating the export of active drugs or functioning as extracellular decoys. Extensive research has focused on understanding the molecular mechanisms underlying the occurrence of resistance and translating these into strategies for early detection. With this review, we want to provide an overview of the current knowledge about the (patho-)biology of exosomes, as well as state-of-the-art methods of isolation and analysis. Furthermore, we highlight the role of exosomes in tumorigenesis and cancer treatment, where they can function as therapeutic agents, biomarkers, and/or targets. By focusing on their roles in therapy resistance, we will reveal new paths of exploiting exosomes for cancer diagnosis and treatment.