Extracellular vesicles (EVs) have emerged as promising tools for cancer diagnosis and therapy owing to their excellent biocompatibility, low immunogenicity, and ability to transport diverse bioactive molecules. This review summarizes recent advances in EVs research, focusing on isolation and detection technologies, their diagnostic and therapeutic applications in oncology, and the key challenges limiting clinical translation. Conventional EVs isolation methods, including ultracentrifugation, density-gradient centrifugation, and polymer-based precipitation, are discussed alongside emerging strategies such as immunoaffinity enrichment, microfluidic separation, lipid-mediated isolation, and thermophoretic enrichment, with comparative evaluation of their yield, purity, cost, and scalability. In cancer diagnosis, EV-associated biomolecules, such as miRNAs, mRNAs, proteins, and lncRNAs, show strong potential as liquid biopsy biomarkers for noninvasive early detection and dynamic disease monitoring. In therapeutic contexts, EVs serve as versatile carriers for gene molecules, chemotherapeutic agents, and small-molecule drugs, and can enhance immunotherapy and RNA-based treatments. Importantly, EVs released from metabolically active tissues, particularly skeletal muscle, contribute to systemic immune regulation and metabolic homeostasis, and their biogenesis and molecular cargo can be influenced by physical activity and exercise-related nutritional status. These insights highlight the need to integrate microengineering technologies, biomolecular profiling, standardized manufacturing systems, and lifestyle-related factors such as exercise and nutrition to accelerate the clinical translation of EV-based strategies in precision oncology and regenerative medicine.

Glioblastoma (GB) is one of the most aggressive brain tumours, with a high mortality rate. Tumour heterogeneity, GB's invasive nature, the blood-brain barrier (BBB) and resistance development offer significant challenges in devising an effective strategy to manage GB. Clinicians rely on tumour resection, radiotherapy and temozolomide (TMZ) chemotherapy, but their efficacy is hindered due to poor BBB penetration. EGFR (epidermal growth factor receptor), NF-κB, angiogenic pathways, RAS/RAF/MAPK, PI3K/Akt/mTOR, etc., play an important role in GB progression. Development in nanotechnology, pharmaceutical science and genetic engineering enables the design of drug candidates with superior efficacy and safety profiles. This review delves into recent advancements in nanoparticles, hydrogels, extracellular vesicles, microneedles and other drug delivery platforms used in GB treatment. These novel drug delivery systems achieved superior BBB penetration, tumour targeting, and controlled release and better survival outcomes in preclinical setups. This review also discusses the major translational challenges, including those of large-scale production, tumour heterogeneity, off-target effects and M2 macrophage induction. Innovative strategies focusing on drug delivery as a biological decision-making process, integrating tumour stress responses into drug carrier and system-level design principles, are discussed, outlining future prospects.

Hedera helix (HE) contains diverse bioactive constituents, including triterpenoid saponins, flavonoids, and phenolic acids, which exhibit various pharmacological activities. In this study, ultrasound-assisted extraction (UAE) combined with natural deep eutectic solvent (NADES) was employed to enhance the extraction efficiency and elucidate the underlying mechanisms. Among the tested formulations, a ternary system composed of malonic acid (Mal), N,N'-dimethylurea (DMU), and 1,4-butanediol (1,4-BDO) achieved the highest efficiency for extracting eight target compounds from the HE leaves. In addition, the key interactions among NADES components were confirmed by Fourier-transform infrared (FT-IR) spectroscopy, providing valuable insights into the extraction mechanism. The UAE process was systematically optimized through single-factor experiments. Subsequently, response surface methodology (RSM) identified the optimal conditions as ultrasonic time of 45 min, solid/liquid ratio of 1:54 g/mL, and ultrasonic temperature of 42 °C. Scanning electron microscopy (SEM) elucidated the microstructural alterations in plant cell walls induced by NADES-UAE, alongside the enhanced penetration and disruption mechanisms. In vitro bioactivity revealed that the NADES-extracted HE exerted strong inhibitory effect on HT-29 colon cancer cells. Overall, these findings demonstrate the high effectiveness and sustainability of NADES-UAE for extracting HE bioactive compounds and provide valuable implications for the industrial-scale production of plant-based functional products.

Radiopharmaceutical therapy (RPT) has emerged as a transformative modality in oncology, particularly for patients with metastatic or inoperable tumors. By leveraging molecularly targeted carriers conjugated to cytotoxic radionuclides, RPT enables precise delivery of ionizing radiation to tumor sites while minimizing off-target effects. Central to this approach are alpha (α) and beta (β) particle-emitting radionuclides. This review aims to provide a comprehensive overview of all clinically relevant alpha and beta emitters and incorporates the most recent advances from 2017-2025, offering a comprehensive and up-to-date perspective. Alpha and beta emitters hold significant promises for the future, especially in nuclear medicine, energy, and environmental monitoring. Medically, these emitters are at the forefront of targeted radiotherapy, offering new hope for cancer treatment. Alpha emitters such as Actinium-225 and Radium-223 are gaining attention for their high linear energy transfer, which allows them to effectively kill cancer cells while minimizing damage to surrounding healthy tissues. Beta emitters, including Lutetium-177 and Iodine-131, are already widely used for treating thyroid cancer, neuroendocrine tumors, and prostate cancer. They offer a longer range in tissue penetration than alpha particles, making them suitable for larger or more diffuse tumors. Alpha and beta emitters hold tremendous promise in targeted radiotherapy. However, current research is limited by an incomplete understanding of resistance pathways, insufficient long-term safety and efficacy data, and underdeveloped personalized treatment frameworks. As production technologies improve and safety protocols advance, these emitters will likely play an even more prominent role in both health care and scientific innovation.

Cerebral Cavernous Malformations (CCMs) are low-flow vascular lesions located within the central nervous system, with a reported prevalence in the general population of 0.16-0.5%. Patients with CCMs may remain asymptomatic or present new onset symptoms such as seizures or focal neurological deficits often related to the occurrence of intracerebral hemorrhage. CCM may appear sporadic or as part of familial forms linked to mutations in the CCM-gene cluster, affecting endothelial cell integrity and triggering molecular cascades, including the MEKK3/KLF2/4 signaling pathway. Recent studies have highlighted the roles of inflammatory, angiogenic, and coagulation pathways alongside the emerging evidence of a gut-brain axis influencing microbiome-driven TLR4 signaling. This systematic review aims to describe molecular biomarkers associated with CCM pathophysiology, emphasizing their potential use as diagnostic and prognostic tools. Circulating plasma biomarkers such as CRP, vitamin D, and interleukins may reflect ongoing inflammatory and endothelial processes, while some imaging biomarkers like Quantitative Susceptibility Mapping (QSM) have shown a correlation with iron deposition and vascular leakage. Leveraging both circulating and imaging biomarkers may improve the therapeutic decision-making process. Further studies are encouraged to validate these findings and to facilitate the development of personalized, evidence-based strategies for the management of CCM.

Epigenetic dysregulation is increasingly recognized as a key driver of glioblastoma (GBM), with bromodomain-containing protein 4 (BRD4) emerging as a critical regulator of tumor malignancy. GBM is an aggressive brain tumor marked by diffuse infiltration, a population of stem-like cells and multiple resistance mechanisms, which together render it largely incurable. Standard treatment, consisting of surgical resection followed by radiotherapy and temozolomide chemotherapy, confers only limited therapeutic benefit, while a member of the bromodomain and extra-terminal (BET) family, BRD4, regulates transcriptional programs essential for oncogene activation, chromatin stability and glioma cell survival. Its expression is markedly elevated in GBM relative to normal brain tissue, implicating BRD4 in tumor initiation, progression and therapeutic resistance. Recent advances have enabled the development of selective BRD4 inhibitors and degraders capable of penetrating the blood-brain barrier and preferentially targeting glioma cells. Preclinical and early-phase clinical studies indicate that these agents suppress tumor growth and may enhance the efficacy of existing treatments. Although BRD4 clearly influences glioma progression and modulates key oncogenic pathways, the precise mechanisms underlying BRD4-driven gliomagenesis remain only partially understood. Ongoing research continues to advance knowledge of its multifaceted functions. This review summarizes current knowledge on BRD4 in GBM, evaluates emerging BRD4-targeted therapeutic strategies and outlines major challenges and future directions for clinical translation.

Colorectal cancer (CRC) continues to represent a substantial worldwide health burden. Accurate risk classification and early detection have a significant impact on prognosis. There is still a significant percentage of patients who are diagnosed at advanced stages, notwithstanding the progress that has been made in screening and treatment. Thus, improved molecular tools that encompass the biological complexity of CRC are needed. High-throughput technologies have expanded the biomarker array for CRC screening, prognosis, and therapeutic prediction. This review summarizes evidence on established and emerging molecular tools from tumor tissue, blood, and stool samples, such as DNA mutations, methylation markers, RNA signatures, circulating tumor DNA (ctDNA), circulating cell-free DNA (cfDNA), extracellular vesicles, and multi-omic composite assays. These provide alternatives to conventional approaches that are relatively less invasive and more sensitive. Prognostic biomarkers-such as RAS, BRAF, HER2 alterations, mismatch repair deficiency, tumor mutational burden, methylation signatures, and non-coding RNAs-provide insight into tumor behavior and recurrence risk. To guide targeted therapies, immunotherapies, and chemotherapy response, predictive biomarkers such as RAS/BRAF mutations, HER2 amplification, MSI-H/dMMR status, POLE/POLD1 mutations, DNA methylation panels, miRNAs, lncRNAs, and liquid biopsy markers are crucial. Emerging technologies such as multi-omics, AI-enhanced biomarker discovery, and novel liquid biopsy components (evDNA, circRNAs) pave the way to precision oncology. These molecular tools have the potential to change how CRC is managed by earlier detection and more precise predictive biomarkers. However, large-scale validation and clinical standardization are still crucial for their extensive utilization.

DNA methylation is an epigenetic modification of the genome, with methylation-based biomarkers showing promise for cancer detection. Quantitative Methylation-Specific PCR (qMSP) is widely used to assess DNA methylation; however, its application to liquid biopsy samples presents technical challenges. Heterogeneity in methylation patterns may impact qMSP accuracy by reducing reliability. This study evaluated the impact of methylation heterogeneity on qMSP performance using synthetic DNA fragments mimicking methylation variation. Additionally, targeted methylation sequencing was performed on prostate cancer tissue and urine samples to examine methylation heterogeneity. The presence of unmethylated CpG sites within the primer and probe regions reduced fluorescence levels and increased Cp values, especially at the 3'-end of primers. The methylation sequencing of genomic DNA from prostate cancer tissue and urine samples revealed the presence of varying methylation patterns, correlating with qMSP outcomes. Tissue samples mainly exhibited fully methylated and fully unmethylated fragments, while urine samples consisted of a higher proportion of partly methylated fragments. The findings suggest that qMSP may not be a reliable method for methylation detection in samples with proportionally high levels of heterogeneous methylated fragments in contrast to fully methylated fragments. This highlights the need for improved DNA methylation analysis in liquid biopsy samples for clinical applications in cancer detection.

Signal transducer and activator of transcription 3 (STAT3) is a central oncogenic hub in several tumors including the Triple-Negative Breast Cancer (TNBC) subtype, where its constitutive activity supports proliferation, metabolic flexibility, tumor progression, immune evasion, and therapeutic resistance. Therapeutic development has largely focused on canonical STAT3 activation driven by tyrosine 705 phosphorylation (p-Y705), which enables dimerization and transcriptional programs. However, accumulating evidence indicates that phosphorylation at serine 727 (p-S727) defines a functionally distinct STAT3 axis, underpinning non-canonical activities across extranuclear compartments that include mitochondria and endoplasmic reticulum/mitochondria-associated membranes. In TNBC, p-S727 STAT3 is frequently prevalent and may sustain oncogenic signaling when p-Y705 is low or pharmacologically suppressed, contributing to metabolic rewiring, redox control, apoptosis resistance, and metastatic fitness. Here, we review the mechanistic basis and clinical correlations of STAT3 p-S727 across cancers with emphasis on TNBC, and discuss how compartmentalized STAT3 pools may integrate kinase signaling, nutrient sensing, and stress responses. We also summarize emerging therapeutic strategies that modulate p-S727-often in conjunction with p-Y705-highlighting proof-of-concept for dual targeting or specific p-S727 to overcome limitations of Y705-centric approaches. Finally, we propose that integrating p-S727/p-Y705 distribution and activity into patient stratification could improve the efficacy-toxicity balance of STAT3-directed therapies in TNBC.

Autophagy and paraptosis are two distinct physiological mechanisms involved in regulating cell fate in cancer. Recent studies have demonstrated that autophagy is a crucial process for maintaining cellular homeostasis by facilitating the removal of misfolded proteins and damaged organelles. However, autophagy is found to play a dual role in cancer. Severe ER and mitochondrial dysfunction can trigger different forms of programmed cell death, including autophagic cell death. In cancer cells that evade apoptosis, paraptosis, a caspase-independent alternate death pathway, is triggered by ER and mitochondrial swelling, leading to extensive cytoplasmic vacuolation. It can be induced by natural compounds, metallic complexes, nanoparticles, or chemotherapeutic agents, primarily through excessive ROS production and disruption of protein, thiol, and calcium/ion homeostasis. Autophagy and paraptosis have been found to be connected through crosstalk. While MAPK activation drives paraptosis, ER stress and the unfolded protein response (UPR) can initiate both paraptosis and autophagy. UPR-mediated PERK activation promotes survival autophagy in ER-stressed melanoma, whereas PERK elimination triggers paraptosis via sec61β with unresolved ER stress. Similarly, CHOP and DDIT4 can enhance ER stress and proteotoxicity, thereby favouring paraptosis. This review is unique in exploring the dynamic interplay between autophagy and paraptosis in cancer cells, highlighting promising therapeutic targets for chemotherapy-resistant cancers.