Glioblastomas (GBMs), among the most aggressive and resilient brain tumors, characteristically exhibit high angiogenic potential, leading to the formation of a dense yet aberrant vasculature, both morphologically and functionally. With these premises, numerous expectations were initially placed on anti-angiogenic therapies, soon dashed by their limited efficacy in concretely improving patient outcomes. Neovascularization in GBM soon emerged as a complex, dynamic, and heterogeneous process, hard to manage with the classical standard of care. Growing evidence has revealed the existence of numerous non-canonical strategies of angiogenesis, variously exploited by GBM to meet its ever-increasing metabolic demand and differently involved in tumor progression, recurrence, and escape from treatments. In this review, we provide an accurate description of each neovascularization mode encountered in GBM tumors to date, highlighting the molecular players and signaling cascades primarily involved. We also detail the key architectural and functional aspects characteristic of the GBM vascular compartment because of an intricate crosstalk between the different angiogenic networks. Additionally, we explore the repertoire of emerging therapies against GBM that are currently under study, concluding with a question: faced with such a challenging scenario, could combined therapies, tailored to the patient’s genetic signatures, represent an effective game changer?

Upper tract urothelial carcinoma (UTUC) is a rare but aggressive malignancy with increasing incidence, often diagnosed at advanced stages due to the limitations of current diagnostic tools. Conventional methods such as urinary cytology, imaging, and ureteroscopy have important drawbacks, including low sensitivity, high costs, and procedural invasiveness. As a result, there is a growing need for non-invasive, highly accurate diagnostic approaches. Epigenetic biomarkers, particularly DNA methylation-based assays, have emerged as promising alternatives for UTUC detection and surveillance. Among these, Bladder EpiCheck® (BE) has shown remarkable sensitivity and specificity, particularly for high-grade tumors, making it a valuable adjunct to standard diagnostic techniques. By analyzing tumor-specific methylation patterns in urine samples, BE offers a practical and non-invasive solution that could improve early detection, reduce the need for ureteroscopy, and enhance risk stratification. Several studies have demonstrated its superior diagnostic accuracy, with sensitivity reaching 97.4 % and specificity up to 100 % for high-grade UTUC. Despite these advantages, challenges remain regarding the standardization of testing protocols, validation in larger patient cohorts, and evaluation of cost-effectiveness. Moreover, the role of DNA methylation biomarkers in guiding clinical decisions and predicting disease progression requires further investigation. This review explores the current state of UTUC diagnosis, compares BE with conventional and emerging biomarkers, and discusses its clinical applications, limitations, and future perspectives. The integration of molecular biomarkers like BE into clinical practice has the potential to revolutionize UTUC diagnosis, improving patient outcomes through more precise, non-invasive detection strategies.

Programmed death-ligand 1 (PD-L1) has become a central biomarker and therapeutic target across multiple solid tumors, yet its clinical meaning in prostate cancer (PCa) remains unsettled. PCa is commonly described as an immunologically ‘cold’ malignancy, characterized by limited baseline cytotoxic T-cell infiltration and a tumor microenvironment (TME) shaped by myeloid-driven suppression and low neoantigen load in many cases. Against this background, PD-L1 expression in PCa is typically low in untreated primary tumors but can increase in aggressive variants, advanced stages, and metastatic castration-resistant disease, where therapy pressure and microenvironmental cues may select for immune-evasive phenotypes. The literature is further complicated by major analytic variability, including differences in antibody clones and platforms, scoring algorithms (tumor proportion score, combined positive score, immune-cell scoring), cut-offs, tissue sites and timing, and pre-analytical variables such as fixation and decalcification. Collectively, available studies suggest that higher PD-L1 expression tends to be associated with adverse clinicopathological features and may enrich for responses to immune checkpoint inhibitors in selected settings, but PD-L1 immunohistochemistry alone is insufficient as a stand-alone predictive tool in unselected patients. This review synthesizes the biological drivers of PD-L1 regulation in PCa, dissects key methodological sources of heterogeneity in PD-L1 assessment, summarizes clinicopathological and therapeutic correlations, and outlines emerging biomarkers and approaches (including mismatch repair deficiency/microsatellite instability, tumor mutational burden, gene-expression signatures, liquid biopsies, and neuro-immune interactions) that may enable more actionable patient stratification.

Inflammatory bowel disease (IBD) represents a heterogenous and complex group of idiopathic chronic inflammatory conditions affecting the gastrointestinal tract and other extraintestinal systems with rising global incidences. The interplay of genetic predisposition and environmental factors contributes to its pathogenesis. Among the key cytokines implicated in IBD molecular alterations, IL-33 stands out for its multifaceted roles in both pathogenesis and repair mechanisms. IL-33, known for its action in initiating immune responses, is closely associated with Th2 immunity and is considered a potent inflammatory factor with dual functions, acting both as a pro-inflammatory cytokine and a transcriptional regulator. Primarily expressed by non-hematopoietic cells in the gastrointestinal tract, IL-33 interacts with its receptor, ST2, to modulate immune responses. In IBD, dysregulated IL-33 expression exacerbates mucosal inflammation, compromising barrier integrity and promoting tissue damage and fibrosis. Additionally, IL-33 plays a complex role in IBD-related colorectal cancer (CRC), affecting tumor progression and angiogenesis. This review summarizes the multifaceted roles of IL-33 in gastrointestinal health and disease, emphasizing its significance in the pathogenesis of IBD and CRC. Moreover, we thought it of interest to provide new insights into potential therapeutic avenues targeting IL-33 signaling for the management of these debilitating conditions.

Aseptic loosening (AL) represents the leading cause of long-term failure in total joint arthroplasty, often necessitating revision surgery. This review explores the complex mechanisms underlying AL, which involve a multifaceted interaction between the implanted biomaterials and the host immune response. We outline the key inflammatory mechanisms triggered by wear debris from polyethylene, polymethylmethacrylate, metal, and ceramic materials. We also examine emerging biomarkers for early detection and differentiation between stable and loosened implants, including proinflammatory cytokines, bone metabolism markers, extracellular matrix degradation products, microRNAs, and genetic polymorphisms. Lastly, we discuss current and future strategies for prevention and treatment, ranging from surgical optimization and biomaterial selection to pharmacological interventions. A comprehensive understanding of these mechanisms may help reduce the incidence of AL and improve long-term outcomes in arthroplasty patients.