Understanding the autophagic functions in cancer stem cell maintenance and therapy resistance.

Complex tumour ecosystem comprising tumour cells and its associated tumour microenvironment (TME) constantly influence the tumoural behaviour and ultimately impact therapy failure, disease progression, recurrence and poor overall survival of patients. Crosstalk between tumour cells and TME amplifies the complexity by creating metabolic changes such as hypoxic environment and nutrient fluctuations. These changes in TME initiate stem cell-like programmes in cancer cells, contribute to tumoural heterogeneity and increase tumour robustness. Recent studies demonstrate the multifaceted role of autophagy in promoting fibroblast production, stemness, cancer cell survival during longer periods of dormancy, eventual growth of metastatic disease and disease resistance. Recent ongoing studies examine autophagy/mitophagy as a powerful survival strategy in response to environmental stress including nutrient deprivation, hypoxia and environmental stress in TME. It prevents irreversible senescence, promotes dormant stem-like state, induces epithelial-mesenchymal transition and increases migratory and invasive potential of tumour cells. The present review discusses various theories and mechanisms behind the autophagy-dependent induction of cancer stem cell (CSC) phenotype. Given the role of autophagic functions in CSC aggressiveness and therapeutic resistance, various mechanisms and studies based on suppressing cellular plasticity by blocking autophagy as a powerful therapeutic strategy to kill tumour cells are discussed.

Exploring the Potential of Ellagic Acid in Gastrointestinal Cancer Prevention: Recent Advances and Future Directions.

Gastrointestinal (GI) cancers are a significant global health concern with diverse etiologies and limited treatment options. Ellagic acid (EA), a natural polyphenolic compound, exhibits promising anticancer properties against various GI malignancies. In this article, we have reviewed recent research on the anticancer potential of EA across esophageal, gastric, colorectal, pancreatic, and liver cancers. In esophageal cancer, EA inhibits the formation of O6-methylguanine (O6-meGua) adducts induced by carcinogens like N-nitrosomethylbenzylamine (NMBA), thereby suppressing tumor growth. Additionally, EA inhibits STAT3 signaling and stabilizes tumor suppressor proteins, showing potential as an anti-esophageal cancer agent. In gastric cancer, EA regulates multiple pathways involved in cell proliferation, invasion, and apoptosis, including the p53 and PI3K-Akt signaling pathways. It also demonstrates anti-inflammatory and antioxidant effects, making it a promising therapeutic candidate against gastric cancer. In colorectal cancer (CRC), EA inhibits cell proliferation, induces apoptosis, and modulates the Wnt/ß-catenin and PI3K/Akt pathways, suggesting its efficacy in preventing CRC progression. Furthermore, EA has shown promise in pancreatic cancer by inhibiting nuclear factor-kappa B, inducing apoptosis, and suppressing epithelial-mesenchymal transition. In liver cancer, EA exhibits radio-sensitizing effects, inhibits inflammatory pathways, and modulates the tumor microenvironment, offering potential therapeutic benefits against hepatocellular carcinoma. Studies on EA potential in combination therapies and the development of targeted delivery systems are required for enhanced efficacy against gastrointestinal cancers.

Decreased plasma gelsolin fosters a fibrotic tumor microenvironment and promotes chemoradiotherapy resistance in esophageal squamous cell carcinoma.

BACKGROUND: Stromal fibrosis is highly associated with therapeutic resistance and poor survival in esophageal squamous cell carcinoma (ESCC) patients. Low expression of plasma gelsolin (pGSN), a serum abundant protein, has been found to correlate with inflammation and fibrosis. Here, we evaluated pGSN expression in patients with different stages of cancer and therapeutic responses, and delineated the molecular mechanisms involved to gain insight into therapeutic strategies for ESCC. METHODS: Circulating pGSN level in ESCC patients was determined by enzyme-linked immunosorbent assay analysis, and the tissue microarray of tumors was analyzed by immunohistochemistry staining. Cell-based studies were performed to investigate cancer behaviors and molecular mechanisms, and mouse models were used to examine the pGSN-induced tumor suppressive effects in vivo. RESULTS: Circulating pGSN expression is distinctively decreased during ESCC progression, and low pGSN expression correlates with poor therapeutic responses and poor survival. Methylation-specific PCR analysis confirmed that decreased pGSN expression is partly attributed to the hypermethylation of the GSN promoter, the gene encoding pGSN. Importantly, cell-based immunoprecipitation and protein stability assays demonstrated that pGSN competes with oncogenic tenascin-C (TNC) for the binding and degradation of integrin αvß3, revealing that decreased pGSN expression leads to the promotion of oncogenic signaling transduction in cancer cells and fibroblasts. Furthermore, overexpression of pGSN caused the attenuation of TNC expression and inactivation of cancer-associated fibroblast (CAF), thereby leading to tumor growth inhibition in mice. CONCLUSIONS: Our results demonstrated that GSN methylation causes decreased secretion of pGSN, leading to integrin dysregulation, oncogenic TNC activation, and CAF formation. These findings highlight the role of pGSN in therapeutic resistance and the fibrotic tumor microenvironment of ESCC.

Tumor microenvironment as a complex milieu driving cancer progression: a mini review.

It has been spotlighted that the Tumor Microenvironment (TME) is crucial for comprehending cancer progression and therapeutic resistance. Therefore, this comprehensive review elucidates the intricate architecture of the TME, which encompasses tumor cells, immune components, support cells, and a myriad of bioactive molecules. These constituents collectively foster dynamic interactions that underpin tumor growth, metastasis, and nuanced responses to anticancer therapies. Notably, the TME's role extends beyond mere physical support, serving as a critical mediator in cancer-cell evolution, immune modulation, and treatment outcomes. Innovations targeting the TME, including strategies focused on the vasculature, immune checkpoints, and T-cell therapies, have forged new pathways for clinical intervention. However, the heterogeneity and complexity of the TME present significant challenges, necessitating deeper exploration of its components and their interplay to enhance therapeutic efficacy. This review underscores the imperative for integrated research strategies that amalgamate insights from tumor biology, immunology, and systems biology. Such an approach aims to refine cancer treatments and improve patient prognoses by exploiting the TME's complexity.

Recent developments in receptor tyrosine kinase inhibitors: A promising mainstay in targeted cancer therapy.

During the past two decades, significant advances have been made in the discovery and development of targeted inhibitors aimed at improving the survival rates of cancer patients. Among the multitude of potential therapeutic targets identified thus far, Receptor Tyrosine Kinases (RTKs) are of particular importance. Dysregulation of RTKs has been implicated in numerous human diseases, particularly cancer, where aberrant signaling pathways contribute to disease progression. RTKs have a profound impact on intra and intercellular communication, and they also facilitate post-translational modifications, notably phosphorylation, which intricately regulates a multitude of cellular processes. Prolonged phosphorylation or the disruption of kinase regulation may lead to significant alterations in cell signaling. The emergence of small molecule kinase inhibitors has revolutionized cancer therapy by offering a targeted and strategic approach that surpasses the efficacy of traditional chemotherapeutic drugs. Over the last two decades, a plethora of targeted inhibitors have been identified or engineered and have undergone clinical evaluation to enhance the survival rates of cancer patients. In this review, we have compared the expression of different RTKs, including Met, KDR/VEGFR2, EGFR, BRAF, BCR, and ALK across different cancer types in TCGA samples. Additionally, we have summarized the recent development of small molecule inhibitors and their potential in treating various malignancies. Lastly, we have discussed the mechanisms of acquired therapeutic resistance with a focus on kinase inhibitors in EGFR mutant and ALK-rearranged non-small cell lung cancer and BCR-ABL positive chronic myeloid leukemia.

The paradox of autophagy in cancer: NEAT1's role in tumorigenesis and therapeutic resistance.

Cancer remains a current active problem of modern medicine, a process during which cell growth and proliferation become uncontrolled. However, the role of autophagy in the oncological processes is counterintuitive and, at the same time, increasingly influential on the formation, development, and response to therapy of oncological diseases. Autophagy is a vital cellular process that removes defective proteins and organelles and supports cellular homeostasis. Autophagy can enhance the ability to form new tumors and suppress this formation in cancer. The dual potential of apoptosis may be the reason for this duality in either promoting or impeding the survival of cancer cells, depending on the situation, including starvation or treatment stress. Furthermore, long non-coding RNA NEAT1, which has been linked to several stages of carcinogenesis and in all forms of the illness, has drawn attention as a major player in cancer biology. NEAT1 is a structural portion of nuclear paraspeckles and has roles in deactivating expression in both transcriptional and post-transcriptional levels. NEAT1 acts in carcinogenesis in numerous ways, comprising interactions with microRNAs, the influence of gene articulation, regulation of epigenetics, and engagement in signalling cascades. In addition, the complexity of NEAT1's role in cancer occurrence is amplified by its place in regulating cancer stem cells and the tumor microenvironment. NEAT1's interaction with autophagy further complicates the already complicated function of this RNA in cancer biology. NEAT1 has been linked to autophagy in several types of cancer, influencing autophagy pathways and altering its stress response and tumor cell viability. Understanding the interrelation between NEAT1, autophagy, and cancer will enable practitioners to identify novel treatment targets and approaches to disrupt oncogenic processes, reduce the occurrence of treatment resistance, and increase patient survival rates. Specialized treatment strategies and regimens are thus achievable. In the present review, the authors analyze sophisticated relationship schemes in cancer: The NEAT1 pathway and the process of autophagy.

Advancements in Understanding the Hide-and-Seek Strategy of Hibernating Breast Cancer Cells and Their Implications in Oncology from a Broader Perspective: A Comprehensive Overview.

Despite recent advancements in technology, breast cancer still poses a significant threat, often resulting in fatal consequences. While early detection and treatments have shown some promise, many breast cancer patients continue to struggle with the persistent fear of the disease returning. This fear is valid, as breast cancer cells can lay dormant for years before remerging, evading traditional treatments like a game of hide and seek. The biology of these dormant breast cancer cells presents a crucial yet poorly understood challenge in clinical settings. In this review, we aim to explore the mysterious world of dormant breast cancer cells and their significant impact on patient outcomes and prognosis. We shed light on the elusive role of the G9a enzyme and many other epigenetic factors in breast cancer recurrence, highlighting its potential as a target for eliminating dormant cancer cells and preventing disease relapse. Through this comprehensive review, we not only emphasise the urgency of unravelling the dynamics of dormant breast cancer cells to improve patient outcomes and advance personalised oncology but also provide a guide for fellow researchers. By clearly outlining the clinical and research gaps surrounding dormant breast cancer cells from a molecular perspective, we aim to inspire further exploration of this critical area, ultimately leading to improved patient care and treatment strategies.

Recent advancements in biomarkers, therapeutics, and associated challenges in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a common type of leukemia that has a high mortality rate. The reasons for high mortality in patients with AML are therapeutic resistance, limited ability to predict duration of response, and likelihood of cancer relapse. Biomarkers, such as leukemic stem cell biomarkers, circulatory biomarkers, measurable residual disease biomarkers, and molecular biomarkers, are used for prognosis, diagnosis, and targeted killing to selectively eliminate AML cells. They also play an indispensable role in providing therapeutic resistance to patients with AML. Therefore, targeting these biomarkers will improve the outcome of AML patients. However, identifying biomarkers that can differentiate between treatment-responsive and non-responsive AML patients remains a challenge. This review discusses recent advancements in AML biomarkers, promising therapeutics, and associated challenges in the treatment of AML.

Glycometabolic reprogramming-induced XRCC1 lactylation confers therapeutic resistance in ALDH1A3-overexpressing glioblastoma.

Patients with high ALDH1A3-expressing glioblastoma (ALDH1A3hi GBM) show limited benefit from postoperative chemoradiotherapy. Understanding the mechanisms underlying such resistance in these patients is crucial for the development of new treatments. Here, we show that the interaction between ALDH1A3 and PKM2 enhances the latter's tetramerization and promotes lactate accumulation in glioblastoma stem cells (GSCs). By scanning the lactylated proteome in lactate-accumulating GSCs, we show that XRCC1 undergoes lactylation at lysine 247 (K247). Lactylated XRCC1 shows a stronger affinity for importin α, allowing for greater nuclear transposition of XRCC1 and enhanced DNA repair. Through high-throughput screening of a small-molecule library, we show that D34-919 potently disrupts the ALDH1A3-PKM2 interaction, preventing the ALDH1A3-mediated enhancement of PKM2 tetramerization. In vitro and in vivo treatment with D34-919 enhanced chemoradiotherapy-induced apoptosis of GBM cells. Together, our findings show that ALDH1A3-mediated PKM2 tetramerization is a potential therapeutic target to improve the response to chemoradiotherapy in ALDH1A3hi GBM.

Examining the evidence for mutual modulation between m6A modification and circular RNAs: current knowledge and future prospects.

The resistance of cancer cells to treatment significantly impedes the success of therapy, leading to the recurrence of various types of cancers. Understanding the specific mechanisms of therapy resistance may offer novel approaches for alleviating drug resistance in cancer. Recent research has shown a reciprocal relationship between circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification, and their interaction can affect the resistance and sensitivity of cancer therapy. This review aims to summarize the latest developments in the m6A modification of circRNAs and their importance in regulating therapy resistance in cancer. Furthermore, we explore their mutual interaction and exact mechanisms and provide insights into potential future approaches for reversing cancer resistance.

NETs: Important players in cancer progression and therapeutic resistance.

Neutrophil extracellular traps (NETs) are web-like structures composed of cytoplasmic contents, DNA chromatin and various granular proteins released by neutrophils in response to viruses, bacteria, immune complexes and cytokines. Studies have shown that NETs can promote the occurrence, development and metastasis of tumors. In this paper, the mechanism underlying the formation and degradation of NETs and the malignant biological behaviors of NETs, such as the promotion of tumor cell proliferation, epithelial mesenchymal transition, extracellular matrix remodeling, angiogenesis, immune evasion and tumor-related thrombosis, are described in detail. NETs are being increasingly studied as therapeutic targets for tumors. We have summarized strategies for targeting NETs or interfering with NET-cancer cell interactions and explored the potential application value of NETs as biomarkers in cancer diagnosis and treatment, as well as the relationship between NETs and therapeutic resistance.

Advances in Non-Small Cell Lung Cancer: Current Insights and Future Directions.

The leading cause of cancer deaths worldwide is attributed to non-small cell lung cancer (NSCLC), necessitating a continual focus on improving the diagnosis and treatment of this disease. In this review, the latest breakthroughs and emerging trends in managing NSCLC are highlighted. Major advancements in diagnostic methods, including better imaging technologies and the utilization of molecular biomarkers, are discussed. These advancements have greatly enhanced early detection and personalized treatment plans. Significant improvements in patient outcomes have been achieved by new targeted therapies and immunotherapies, providing new hope for individuals with advanced NSCLC. This review discusses the persistent challenges in accessing advanced treatments and their associated costs despite recent progress. Promising research into new therapies, such as CAR-T cell therapy and oncolytic viruses, which could further revolutionize NSCLC treatment, is also highlighted. This review aims to inform and inspire continued efforts to improve outcomes for NSCLC patients globally, by offering a comprehensive overview of the current state of NSCLC treatment and future possibilities.

Exploring the multifaceted role of obesity in breast cancer progression.

Obesity is a multifaceted metabolic disorder characterized by excessive accumulation of adipose tissue. It is a well-established risk factor for the development and progression of breast cancer. Adipose tissue, which was once regarded solely as a passive energy storage depot, is now acknowledged as an active endocrine organ producing a plethora of bioactive molecules known as adipokines that contribute to the elevation of proinflammatory cytokines and estrogen production due to enhanced aromatase activity. In the context of breast cancer, the crosstalk between adipocytes and cancer cells within the adipose microenvironment exerts profound effects on tumor initiation, progression, and therapeutic resistance. Moreover, adipocytes can engage in direct interactions with breast cancer cells through physical contact and paracrine signaling, thereby facilitating cancer cell survival and invasion. This review endeavors to summarize the current understanding of the intricate interplay between adipocyte-associated factors and breast cancer progression. Furthermore, by discussing the different aspects of breast cancer that can be adversely affected by obesity, this review aims to shed light on potential avenues for new and novel therapeutic interventions.

The Role of Mesenchymal Reprogramming in Malignant Clonal Evolution and Intra-Tumoral Heterogeneity in Glioblastoma.

Glioblastoma (GBM) is the most common yet uniformly fatal adult brain cancer. Intra-tumoral molecular and cellular heterogeneities are major contributory factors to therapeutic refractoriness and futility in GBM. Molecular heterogeneity is represented through molecular subtype clusters whereby the proneural (PN) subtype is associated with significantly increased long-term survival compared to the highly resistant mesenchymal (MES) subtype. Furthermore, it is universally recognized that a small subset of GBM cells known as GBM stem cells (GSCs) serve as reservoirs for tumor recurrence and progression. The clonal evolution of GSC molecular subtypes in response to therapy drives intra-tumoral heterogeneity and remains a critical determinant of GBM outcomes. In particular, the intra-tumoral MES reprogramming of GSCs using current GBM therapies has emerged as a leading hypothesis for therapeutic refractoriness. Preventing the intra-tumoral divergent evolution of GBM toward the MES subtype via new treatments would dramatically improve long-term survival for GBM patients and have a significant impact on GBM outcomes. In this review, we examine the challenges of the role of MES reprogramming in the malignant clonal evolution of glioblastoma and provide future perspectives for addressing the unmet therapeutic need to overcome resistance in GBM.

Association between methyltransferase-like 3 and non-small cell lung cancer: pathogenesis, therapeutic resistance, and clinical applications.

Non-small cell lung cancer (NSCLC) is a malignant cancer that with high incidence, recurrence, and mortality rates in human beings, posing significant threats to human health. Moreover, effective early diagnosis of NSCLC remains limited primarily by the lack of accurate biomarkers. Therefore, there is an urgent need to understand the mechanisms underlying NSCLC pathogenesis and treatment failure. Methyltransferase-like 3 (METTL3) is a prototypical member of a family of which its members transfer methyl groups. It has been implicated in modulating the pathogenesis of NSCLC, as well as conferring resistance to NSCLC therapeutics. The targeting of METTL3 for NSCLC treatment has been reported. However, the relationship between METTL3 and NSCLC remains to be demonstrated. In this review, we discuss relevant interrelationships by summarising the studies on METTL3 in NSCLC pathogenesis, therapeutic resistance, and clinical applications. Current research suggests that the upregulation of METTL3 expression propels the tumorigenesis, progression, and treatment resistance of NSCLC. Therefore, we propose that METTL3 is an excellent candidate biomarker for NSCLC diagnosis and prognosis. Therapeutic targeting of METTL3 has significant potential for NSCLC treatment. This review provides a summary of the association between METTL3 and NSCLC, which would be a valuable reference for both basic and clinical research.

The Protective Role of miR-125b in Hepatocellular Carcinoma: Unraveling Tumor-Suppressive Mechanisms.

MicroRNAs (miRNAs) have emerged as crucial regulators of gene expression, playing pivotal roles in various biological processes, including cancer development and progression. Among them, miR-125b has garnered significant attention due to its multifaceted functional roles in human hepatocellular carcinoma (HCC). Extensive research has revealed that miR-125b plays a dual role in HCC, acting as both a tumor suppressor and an oncogene depending on the context. As a tumor suppressor, miR-125b exerts its inhibitory effects on HCC by targeting key oncogenic pathways and genes involved in cell proliferation, migration, invasion, and angiogenesis. Its downregulation in HCC is frequently observed and correlates with aggressive tumor characteristics and poor prognosis. Conversely, miR-125b can also function as an oncogene in specific HCC subtypes or under certain conditions. It has been shown to promote HCC growth, metastasis, and therapeutic resistance by targeting tumor suppressor genes, modulating the epithelial-mesenchymal transition (EMT) process, and enhancing cancer stem cell-like properties. The upregulation of miR-125b in HCC has been associated with advanced disease stages and unfavorable clinical outcomes. Furthermore, the dysregulation of miR-125b expression in HCC is influenced by a complex network of regulatory mechanisms. Understanding these regulatory mechanisms is crucial for deciphering the precise functional roles of miR-125b in HCC and exploring its potential as a diagnostic biomarker or therapeutic target. In the current review study, we comprehensively elucidated the diverse functional roles of miR-125b in HCC, providing a comprehensive overview of its regulatory mechanisms and impact on key cellular processes involved in HCC progression.

The CDK9 inhibitor enitociclib overcomes resistance to BTK inhibition and CAR-T therapy in mantle cell lymphoma.

Inhibitors of Bruton's tyrosine kinase (BTKi) and chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 are paradigm-shifting advances in treating patients with aggressive mantle cell lymphoma (MCL). However, clinical relapses following BTKi and CD19-directed CAR-T treatments are a fast-growing medical challenge. Development of novel therapies to overcome BTKi resistance (BTKi-R) and BTKi-CAR-T dual resistance (Dual-R) are urgently needed. Our single-cell RNA sequencing data revealed major transcriptomic reprogramming, with great enrichment of MYC-targets evolving as resistance to these therapies developed. Interestingly, cyclin-dependent kinase 9 (CDK9), a critical component of the positive transcription elongation factor-b complex, was among the top upregulated genes in Dual-R vs. BTKi-R samples. We therefore hypothesized that targeting CDK9 may turn off MYC-driven tumor survival and drug resistance. Enitociclib (formerly VIP152) is a selective CDK9 inhibitor whose potency against MCL has not been assessed. In this study, we found that enitociclib was highly potent in targeting lymphoma cells, with the half-maximal inhibitory concentration (IC50) ranging from 32 to 172 nM in MCL and diffuse large B-cell lymphoma cell lines. It inhibited CDK9 phosphorylation and downstream events including de novo synthesis of the short-lived proteins c-MYC, MCL-1, and cyclin D1, and induced apoptosis in a caspase-3-dependent manner. Enitociclib potently inhibited in vivo tumor growth of cell line-derived and patient-derived xenografts having therapeutic resistance. Our data demonstrate the potency of enitociclib in overcoming therapeutic resistance in MCL models and provide evidence in favor of its clinical investigation.

Extracellular Vesicles in Breast Cancer: From Intercellular Communication to Therapeutic Opportunities.

Breast cancer, a multifaceted and heterogeneous disease, poses significant challenges in terms of understanding its intricate resistance mechanisms and devising effective therapeutic strategies. This review provides a comprehensive overview of the intricate landscape of extracellular vesicles (EVs) in the context of breast cancer, highlighting their diverse subtypes, biogenesis, and roles in intercellular communication within the tumour microenvironment (TME). The discussion spans various aspects, from EVs and stromal cells in breast cancer to their influence on angiogenesis, immune response, and chemoresistance. The impact of EV production in different culture systems, including two dimensional (2D), three dimensional (3D), and organoid models, is explored. Furthermore, this review delves into the therapeutic potential of EVs in breast cancer, presenting emerging strategies such as engineered EVs for gene delivery, nanoplatforms for targeted chemotherapy, and disrupting tumour derived EVs as a treatment approach. Understanding these complex interactions of EV within the breast cancer milieu is crucial for identifying resistance mechanisms and developing new therapeutic targets.

Optimizing cancer therapy: a review of the multifaceted effects of metronomic chemotherapy.

Metronomic chemotherapy (MCT), characterized by the continuous administration of chemotherapeutics at a lower dose without prolonged drug-free periods, has garnered significant attention over the last 2 decades. Extensive evidence from both pre-clinical and clinical settings indicates that MCT induces distinct biological effects than the standard Maximum Tolerated Dose (MTD) chemotherapy. The low toxicity profile, reduced likelihood of inducing acquired therapeutic resistance, and low cost of MCT render it an attractive chemotherapeutic regimen option. One of the most prominent aspects of MCT is its anti-angiogenesis effects. It has been shown to stimulate the expression of anti-angiogenic molecules, thereby inhibiting angiogenesis. In addition, MCT has been shown to decrease the regulatory T-cell population and promote anti-tumor immune response through inducing dendritic cell maturation and increasing the number of cytotoxic T-cells. Combination therapies utilizing MCT along with oncolytic virotherapy, radiotherapy or other chemotherapeutic regimens have been studied extensively. This review provides an overview of the current status of MCT research and the established mechanisms of action of MCT treatment and also offers insights into potential avenues of development for MCT in the future.

Extracellular vesicles in neuroblastoma: role in progression, resistance to therapy and diagnostics.

Neuroblastoma (NB) is the most common extracranial solid pediatric cancer, and is one of the leading causes of cancer-related deaths in children. Despite the current multi-modal treatment regimens, majority of patients with advanced-stage NBs develop therapeutic resistance and relapse, leading to poor disease outcomes. There is a large body of knowledge on pathophysiological role of small extracellular vesicles (EVs) in progression and metastasis of multiple cancer types, however, the importance of EVs in NB was until recently not well understood. Studies emerging in the last few years have demonstrated the involvement of EVs in various aspects of NB pathogenesis. In this review we summarize these recent findings and advances on the role EVs play in NB progression, such as tumor growth, metastasis and therapeutic resistance, that could be helpful for future investigations in NB EV research. We also discuss different strategies for therapeutic targeting of NB-EVs as well as utilization of NB-EVs as potential biomarkers.