Search Results (279)

Glioblastoma (GB) is one of the most aggressive and invasive cancers. Current treatment protocols for GB include surgical resection, radiotherapy, and chemotherapy with temozolomide. However, despite these treatments, physicians still struggle to effectively image, diagnose, and treat GB. As such, patients frequently experience recurrence of GB, demanding innovative strategies for early detection and effective therapy. Bioconjugated quantum dots (QDs) have emerged as powerful nanoplatforms for precision imaging and targeted drug delivery due to their unique optical properties, tunable size, and surface versatility. Due to their extremely small size, QDs can cross the blood–brain barrier and be used for precision imaging of GB. This review explores the integration of QDs with click chemistry for robust bioconjugation, focusing on artificial intelligence (AI) to advance GB therapy, mechanistic insights into cellular uptake and signaling, and strategies for mitigating toxicity. Click chemistry enables site-specific and stable conjugation of targeting ligands, peptides, and therapeutic agents to QDs, enhancing selectivity and functionalization. Algorithms driven by AI may facilitate predictive modeling, image reconstruction, and personalized treatment planning, optimizing QD design and therapeutic outcomes. We discuss molecular mechanisms underlying interactions of QDs with GB, including receptor-mediated endocytosis and intracellular trafficking, which influence biodistribution and therapeutic efficacy. Use of QDs in photodynamic therapy, which uses reactive oxygen species to induce apoptotic cell death in GB cells, is an innovative therapy that is covered in this review. Finally, this review addresses concerns associated with the toxicity of metal-based QDs and highlights how QDs can be coupled with AI to develop new methods for precision imaging for detecting and treating GB for induction of apoptosis. By converging nanotechnology and computational intelligence, bioconjugated QDs represent a transformative platform for paving a safer path to smarter and more effective clinical interventions of GB. Full article

Glioblastoma, isocitrate dehydrogenase (IDH1/2) wild-type (IDH-wildtype), is one of the most aggressive and malignant tumors of the central nervous system, characterized by rapid growth, pronounced cellular heterogeneity, and an exceptionally poor prognosis. The median survival time for patients with glioblastoma, IDH-wildtype, is approximately 15 months after diagnosis, and current multimodal treatment strategies remain largely ineffective. This review focuses on contemporary pharmacotherapeutic approaches used in the management of glioblastoma, IDH-wildtype, including temozolomide-based chemotherapy, corticosteroids for edema control, and antiangiogenic therapy in recurrent disease, with particular emphasis on their clinical efficacy and limitations. In addition, the review discusses emerging targeted therapeutic strategies developed for IDH-mutant diffuse gliomas, which represent a biologically distinct disease entity. Particular attention is given to ivosidenib, a selective inhibitor of mutant IDH1, currently evaluated for the treatment of astrocytoma, IDH-mutant, grade 4. Its epigenetic mechanism of action, involving inhibition of the oncometabolite 2-hydroxyglutarate (2-HG), is outlined, along with preliminary clinical evidence suggesting potential to delay disease progression. Finally, innovative drug-delivery technologies designed to overcome the blood–brain barrier are briefly discussed as complementary strategies that may enhance the efficacy of both conventional and targeted therapies. Overall, future advances in the treatment of diffuse gliomas will likely depend on the integration of molecularly targeted agents, predictive biomarkers, and advanced delivery platforms aimed at improving patient survival and quality of life. Full article

Glioblastoma (GBM), the most common, invasive, and chemoresistant form of adult primary brain cancer, is characterized by rapid cell proliferation, local invasiveness, and resistance to chemotherapy (e.g., temozolomide (TMZ)) and radiation therapy. Curcumin, a bioactive polyphenol derived from Curcuma longa, has exhibited exceptional anti-cancer properties, including anti-proliferative, pro-apoptotic, anti-inflammatory, and anti-angiogenic activities in a wide range of cancer models, including GBM. However, the clinical application of curcumin has been seriously limited by several challenges, including low water solubility, low bioavailability, rapid systemic clearance, and poor blood–brain barrier (BBB) penetration. To overcome these challenges, several nanocarrier systems to produce nanocurcumin have been developed, including liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, and micelles. These nanoformulations improve the solubility, stability, systemic circulation, and target-directed delivery of curcumin to glioma cells, thereby resulting in a high level of accumulation in the glioma microenvironment. On the other hand, this work is devoted to the potential of curcumin and nanocurcumin for the treatment of GBM. The article provides a detailed review of the major molecular targets of curcumin, such as NF-κB, STAT3, PI3K/AKT/mTOR, and p53 signaling pathways, as well as recent advancements in nanotechnology-based delivery platforms that improve drug delivery across the BBB and their possible clinical translation. We also include a thorough examination of the issues, limitations, and potential opportunities associated with the clinical advancement of curcumin-based therapeutics for GBM. Full article

Temozolomide (TMZ) remains foundational in the management of adult-type diffuse gliomas in general, and glioblastoma specifically. However, its efficacy harbors an evolutionary trade-off. TMZ drives its cytotoxicity through generating O⁶-methylguanine lesions, especially active in MGMT-silenced, mismatch repair (MMR)-proficient tumors. By selecting for acquired MMR-deficient subclones, often via MSH6 inactivation, this process escalates into a hypermutator phenotype, generating thousands of de novo alterations. This is a hallmark of the mutational signature known as SBS11, characterized by C>T transitions, which is associated with TMZ treatment. The hypermutator phenotype drives heterogeneity, therapeutic resistance, spatial diversification, and distant recurrence. Despite harboring a mutational burden comparable to melanoma and lung cancer, TMZ-induced hypermutation does not sensitize gliomas to immune checkpoint blockade. This resistance reflects the profoundly immunosuppressive brain microenvironment, impaired antigen presentation, marked transcriptional plasticity, and perhaps also the frequent use of corticosteroids. Emerging strategies aim to exploit vulnerabilities created by TMZ-mediated genomic instability, including PARP, ATR, WEE1, and AURKA inhibition; alternative alkylators; metabolic rewiring; and G-quadruplex stabilization. Notably, the real-time detection of evolving mutational signatures via CSF-based liquid biopsies may enable adaptive therapy before radiographic progression. By reframing TMZ as a potent evolutionary agent rather than a conventional chemotherapy, this review synthesizes recent mechanistic insights and translational opportunities to guide a next-generation, evolution-informed treatment paradigm for glioma. Full article

Glioblastoma (GBM) represents a highly invasive primary malignant tumor within the central nervous system (CNS). Temozolomide (TMZ), a first-line chemotherapy agent for GBM treatment, has significant limitations, including drug resistance, poor water solubility, a short half-life, and notable toxic side effects. The innovation of the TMZ dosage form is pivotal for enhancing its therapeutic efficacy. In this study, solid lipid nanoparticles (SLN) loaded with Angiopep-2 (A2) and TMZ (TMZ-A2SLN), a nanopolymer featuring a solid spherical morphology and a particle size of approximately 100 nm, were constructed. The combined effect of TMZ-A2SLN and small-interfering RNA (siRNA) that can knock down the expression of the HOXB9 gene (siHOXB9) augmented the sensitivity of the glioma cell line U251 to TMZ. Under the combined effect, the viability of U251 cells was reduced by 77%. Meanwhile, the mortality rate increased by approximately 45%, and the cell apoptosis rate rose by around 36%. The number of cells arrested in the G2/M and S phases rose. Proteomic analysis indicates that TMZ-A2SLN might be implicated in the pro-inflammatory signaling cascade, tumor migration, invasion, and angiogenesis during the treatment of glioma cells. Moreover, HOXB9 may play a crucial regulatory role in the PPAR signaling pathway, the neural signaling pathway, the phospholipase D signaling pathway, the IL-17 signaling pathway, mineral absorption, and other pathways during glioma cell treatment. Full article

Glioblastoma (GBM) is one of the most common and aggressive primary malignant tumors of the central nervous system, accounting for about half of all gliomas in adults. Despite intensive research and advances in molecular biology, genomics, and modern neuroimaging techniques, the prognosis for patients with GBM remains extremely poor. Despite the implementation of multimodal treatment involving surgery, radiotherapy, and chemotherapy with temozolomide, the average survival time of patients is only about 15 months. This is primarily due to the complex biology of this cancer, which involves numerous genetic and epigenetic abnormalities, as well as a highly heterogeneous tumor structure and the presence of glioblastoma stem cells with self renewal capacity. Mutations and abnormalities in genes such as IDH-wt, EGFR, PTEN, TP53, TERT, and CDKN2A/B are crucial in the pathogenesis of GBM. In particular, IDH-wt status (wild-type isocitrate dehydrogenase) is one of the most important identification markers distinguishing GBM from other, more favorable gliomas with IDH mutations. Frequent EGFR amplifications and TERT gene promoter mutations lead to the deregulation of tumor cell proliferation and increased aggressiveness. In turn, the loss of function of suppressor genes such as PTEN or CDKN2A/B promotes uncontrolled cell growth and tumor progression. The immunosuppressive tumor microenvironment also plays an important role, promoting immune escape and weakening the effectiveness of systemic therapies, including immunotherapy. The aim of this review is to summarize the current state of knowledge on the epidemiology, classification, pathogenesis, diagnosis, and treatment of glioblastoma multiforme, as well as to discuss the impact of recent advances in molecular and imaging diagnostics on clinical decision-making. A comprehensive review of recent literature (2018–2025) was conducted, focusing on WHO CNS5 classification updates, novel biomarkers (IDH, TERT, MGMT, EGFR), and modern diagnostic techniques such as liquid biopsy, radiogenomics, and next-generation sequencing (NGS). The results of the review indicate that the introduction of integrated histo-molecular diagnostics in the WHO 2021 classification has significantly increased diagnostic precision, enabling better prognostic and therapeutic stratification of patients. Modern imaging techniques, such as advanced magnetic resonance imaging (MRI), positron emission tomography (PET), and radiomics and radiogenomics tools, allow for more precise assessment of tumor characteristics, prediction of response to therapy, and monitoring of disease progression. Contemporary molecular techniques, including DNA methylation profiling and NGS, enable in-depth genomic and epigenetic analysis, which translates into a more personalized approach to treatment. Despite the use of multimodal therapy, which is based on maximum safe tumor resection followed by radiotherapy and temozolomide chemotherapy, recurrence is almost inevitable. GBM shows a high degree of resistance to treatment, which results from the presence of stem cell subpopulations, dynamic clonal evolution, and the ability to adapt to unfavorable microenvironmental conditions. Promising preclinical and early clinical results show new therapeutic strategies, including immunotherapy (cancer vaccines, checkpoint inhibitors, CAR-T therapies), oncolytic virotherapy, and Tumor Treating Fields (TTF) technology. Although these methods show potential for prolonging survival, their clinical efficacy still needs to be confirmed in large studies. The role of artificial intelligence in the analysis of imaging and molecular data is also increasingly being emphasized, which may contribute to the development of more accurate predictive models and therapeutic decisions. Despite these advancements, GBM remains a major therapeutic challenge due to its high heterogeneity and treatment resistance. The integration of molecular diagnostics, artificial intelligence, and personalized therapeutic strategies that may enhance survival and quality of life for GBM patients. Full article

Background: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by limited therapeutic options and poor prognosis. Temozolomide (TMZ) remains the standard chemotherapy; however, its effectiveness is often hindered by the development of acquired resistance. Cuproptosis, a recently identified copper-dependent form of regulated cell death, has emerged as a potential therapeutic target. The synergistic effects of TMZ and copper, as well as the molecular mechanisms underlying their combined action, remain unclear. This study aimed to investigate the role of tripartite motif-containing protein 14 (TRIM14) and its downstream effector ATP7A in mediating TMZ- and copper-induced cuproptosis in glioma. Methods: We employed in vitro cellular assays, in vivo xenograft models, bioinformatic analysis, immunofluorescence staining, Western blotting, and co-immunoprecipitation experiments to examine the functional involvement of TRIM14 and ATP7A during combined TMZ and copper chloride (CuCl₂) treatment. Intracellular copper levels and cuproptosis markers, including Dihydrolipoamide S-acetyltransferase (DLAT), were assessed to evaluate copper-dependent cytotoxicity. Results: TMZ combined with CuCl₂ markedly enhanced cuproptosis in glioma cells, as evidenced by increased DLAT expression and elevated intracellular copper accumulation. This combination treatment significantly suppressed TRIM14 expression, downregulated the TRIM14–ATP7A axis, and inhibited non-canonical NF-κB signaling. Co-immunoprecipitation assays further revealed a potential interaction between TRIM14 and ATP7A, suggesting that TRIM14 may modulate ATP7A stability or activity. Conclusions: Our findings indicate that TMZ and copper synergistically induce cuproptosis in GBM by disrupting the TRIM14–ATP7A regulatory axis and promoting intracellular copper accumulation. Targeting TRIM14 or ATP7A to enhance cuproptosis may represent a promising therapeutic strategy to overcome TMZ resistance and improve clinical outcomes in GBM patients. Full article

Metastatic or unresectable pheochromocytomas and paragangliomas (PPGLs) remain rare but clinically challenging neuroendocrine neoplasms with limited curative options. Traditionally managed with surgery, radionuclide therapy, or cytotoxic chemotherapy, systemic treatments have historically achieved disease stabilization, rather than durable remissions. In recent years, however, the therapeutic landscape has evolved substantially. Radiopharmaceuticals such as ¹³¹I-MIBG and ¹⁷⁷Lu-DOTATATE continue to play a pivotal role, achieving disease control in many patients. Cytotoxic regimens, particularly temozolomide, remain relevant, with some studies suggesting that SDHB-mutated PPGLs demonstrate a heightened sensitivity associated with MGMT promoter hypermethylation and reduced MGMT expression. Targeted agents are increasingly important: multi-kinase inhibitors such as sunitinib, anlotinib, and cabozantinib have shown meaningful activity. The landmark approval of belzutifan, a HIF-2α inhibitor, in 2025 represents the first oral targeted therapy for advanced/metastatic PPGL, which is particularly relevant for pseudohypoxic Cluster 1 tumors. Immunotherapy has yielded modest responses with checkpoint inhibitor monotherapy, but ongoing studies of dual checkpoint blockade and TKI–ICI combinations hold promise. Novel approaches, including PARP inhibition, metabolic targeting strategies, and cancer vaccines, are under investigation, especially for aggressive SDHB-related disease. Optimal sequencing of these therapies is emerging as a central challenge, with treatment strategies increasingly tailored to molecular genotype, tumor behavior, and functional imaging phenotype. This review summarizes current evidence and highlights ongoing clinical trials, underscoring a paradigm shift toward precision medicine and rational combination strategies. Collectively, these advances bring cautious optimism that metastatic PPGLs may soon become a more manageable chronic disease with improved survival and quality of life. Full article

Resistance to alkylating chemotherapeutic agents such as temozolomide (TMZ) is a significant challenge in treating tumors with high MGMT expression, including MGMT-positive glioblastoma and neuroendocrine neoplasms. In this study, we investigated the effect of RNA-binding motif protein 39 (RBM39) downregulation on MGMT protein levels, based on prior observations suggesting an association between these two proteins. Pharmacological depletion or siRNA-mediated knockdown of RBM39 led to a marked reduction in MGMT protein levels in MGMT-expressing cancer cells. We further showed that dual targeting of RBM39 (using indisulam) and MGMT (with O6-benzylguanine) synergistically enhanced MGMT depletion. Functionally, combined indisulam and TMZ treatment significantly increased apoptosis and decreased clonogenic growth in neuroendocrine tumor cells. These findings identify MGMT as a downstream target of RBM39 in MGMT-expressing cancer cells and highlight the therapeutic potential of co-targeting RBM39 and MGMT to overcome resistance to alkylating chemotherapy. Full article

Background: Pancreatic neuroendocrine tumor (pNET) is a rare and complex disease that requires careful management and treatment. Currently, a range of treatments, including surgery, somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT), targeted drugs, cytotoxic chemotherapy, and immunotherapy, exist for pNETs. However, determining the optimal treatment strategies remains challenging. Aim: To evaluate the efficacy and safety of non-surgical therapies, such as somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT), targeted drugs, cytotoxic chemotherapy, and immunotherapy in treating pNETs. Methods: We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science databases for relevant studies published from inception until August 2025. Randomized clinical trials (RCTs), non-randomized clinical trials, and prospective studies were included in this meta-analysis if they evaluated the efficacy and safety of any treatment of interest in patients with pNETs. Results: Thirty-three studies involving 2374 pNET patients were analyzed. Targeted therapies showed modest objective response rates (ORRs) but high disease control rates (DCRs): everolimus (ORR 7%, 95% CI: 3–10%; DCR 81%, 95% CI: 75–87%), sunitinib (ORR 12%, 95% CI: 5–19%; DCR 79%, 95% CI: 70–88%), surufatinib (ORR 19%, 95% CI: 12–27%; DCR 81%, 95% CI: 73–89%). Cytotoxic chemotherapy demonstrated higher ORRs: dacarbazine-based (32%, 95% CI: 21–43%), streptozocin-based (40%, 95% CI: 25–54%), temozolomide-based (42%, 95% CI: 29–55%). PRRT showed varying efficacy: ¹⁷⁷Lu-DOTATATE (ORR 36%, 95% CI: 27–44%; DCR 84%, 95% CI: 76–92%), ⁹⁰Y-DOTATOC (ORR 27%, 95% CI: 18–36%; DCR 73%, 95% CI: 63–83%). SSAs had low ORRs but high DCRs: lanreotide (ORR 0%, DCR 67%, 95% CI: 57–77%), octreotide (ORR 23%, 95% CI: 15–31%; DCR 75%, 95% CI: 66–84%). Immunotherapy with pembrolizumab showed limited efficacy (ORR 7%, 95% CI: 0–14%). Treatment-related adverse events were common across therapies, with specific toxicity profiles for each modality. Conclusions: Cytotoxic chemotherapy offers better response rates than other treatment modalities. However, toxicity management is crucial. PRRT also shows robust antitumor activity and disease control, while SSAs and targeted therapies are effective treatment options for disease stabilization. Immunotherapy demonstrated limited antitumor activity, and further research is needed to establish its role in pNET treatment. Full article

Glioblastoma (GBM) is an aggressive and common form of central nervous system primary malignant tumor in adults. GBM accounts for about half of all gliomas. Despite maximal resection, radiotherapy, and temozolomide, median survival is still 12–15 months because of tumor heterogeneity, diffuse infiltration, and therapeutic resistance. Recurrence is nearly universal, underscoring the need for novel therapies. Oncolytic virotherapy demonstrates a promising strategy that combines direct tumor cell lysis with immune activation. Tumor-selective viruses replicate within malignant cells, induce cell death, and release tumor antigens, thereby reshaping the immunosuppressive microenvironment. Several viral backbones have advanced to clinical testing, including adenovirus (DNX-2401), herpes simplex virus (G47Δ, G207), poliovirus (PVS-RIPO), measles virus (MV-CEA), reovirus (pelareorep), vaccinia virus (Pexa-Vec), and vesicular stomatitis virus (VSV-GP). The approval of G47Δ in Japan for malignant glioma marks a milestone, with early trials demonstrating safety and signals of durable benefit, particularly in combination regimens. Current research emphasizes engineering viral genomes to enhance selectivity, immune stimulation, and resistance to clearance, while exploring synergistic combinations with radiotherapy, chemotherapy, immune checkpoint inhibitors, and tumor-treating fields. Advances in delivery, such as convection-enhanced infusion and blood–brain barrier modulation, are also under investigation. Despite obstacles, oncolytic virotherapy holds significant potential within multimodal GBM strategies. Full article

Background: Glioblastoma (GBM) patients exhibit a median overall survival of 12–18 months post-diagnosis, with disease recurrence typically emerging within 6–9 months. Due to the absence of standardized therapeutic protocols at recurrence, management is highly individualized. This study comprehensively evaluates overall survival (OS) time to subsequent progression, and clinical status evolution following diverse interventions for first GBM recurrence. Methods: Data from 350 patients were retrospectively analyzed. The entire cohort was divided into the following four groups: (A) patients with no further therapy at recurrence, (B) combined re-radiation and chemotherapy with temozolomide with or without lomustine or other individual medication, (C) surgery without re-adjuvant treatment, and (D) surgery and at least one cycle of chemotherapy or re-radiation or a combination. Statistical analyses were performed using non-parametric tests. Additionally, various regression analyses were performed. Results: Patients receiving invasive therapeutic regimens with or without adjuvant re-therapy (groups C and D) demonstrated significantly prolonged OS (p < 0.001) alongside superior Karnofsky performance status (KPS) at both 3-month (p = 0.016) and 6-month (p < 0.001) intervals post-intervention. Multivariate analysis confirmed surgical resection, temozolomide (TMZ) chemotherapy, and radiotherapy as independent positive predictors of OS (respective p-values: <0.001, <0.001, and 0.048). Notably, surgical resection significantly improved clinical status (p < 0.001), whereas radiotherapy had a significant negative effect on clinical status (p = 0.016). Conclusions: Contrary to the prevailing hypothesis that survival extension through extensive therapy at recurrence necessitates compromised clinical status, our findings demonstrate that contemporary recurrence therapies—particularly multimodal approaches—simultaneously enhance both OS and functional outcomes in GBM patients. This paradigm challenges conventional expectations of therapeutic trade-offs at disease recurrence. Full article

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of malignancies characterized by varying degrees of aggressiveness and clinical behavior. Despite advancements in treatment, including targeted therapies such as sunitinib and everolimus, peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE, and chemotherapy regimens like capecitabine plus temozolomide, the advanced GEP-NETs remain largely incurable. The limited efficacy of current treatments highlights the urgent need for novel therapeutic strategies. Recent years have seen a rise in several landmark clinical trials aimed at exploring new agents and combinations to improve patient outcomes in GEP-NETs. This literature review focuses on the ongoing clinical trials that hold promise for advancing the treatment landscape of GEP-NETs. We include some industry- and cooperative group-sponsored, phase II-III, randomized, and comparative trials in our review. We analyze the design, rationale, objectives, and preliminary findings of these trials, with a particular emphasis on those with pending results that may offer new insights into potential therapeutic targets. By examining these trials, we aim to provide a comprehensive overview of the evolving strategies in the management of GEP-NETs and underscore the importance of continued research innovation in addressing the challenges posed by the heterogeneity of GEP-NETs and in the pursuit of more effective and potentially curative treatment options. Full article

Glioblastoma (GBM) is an aggressive and highly heterogeneous tumor that frequently recurs despite surgery followed by radio-chemotherapy and, more recently, TTFields. This recurrence is largely driven by glioblastoma stem cells (GSCs), which are intrinsically resistant to standard therapies. Identifying molecular targets that underlie this resistance is therefore critical. Here, we investigated whether the inhibition of FGFR1, previously identified as a key mediator of GBM radioresistance, using pemigatinib, a selective FGFR1–3 inhibitor, could enhance GSC radiosensitivity in vitro and in vivo. Pemigatinib treatment inhibited FGFR1 signaling, promoted proteasome-dependent FGFR1 degradation, and reduced the viability, neurosphere formation, and sphere size in GSCs with unmethylated MGMT, a subgroup known for poor response to standard treatments. In MGMT-unmethylated differentiated GBM cell lines, pemigatinib combined with temozolomide further enhanced radiosensitivity. Transcriptomic analysis revealed that pemigatinib treatment led to the downregulation of S100A4, a biomarker associated with mesenchymal transition, angiogenesis, and immune modulation in GBM. Functional studies confirmed that silencing S100A4 significantly improved GSCs’ response to irradiation. In vivo, pemigatinib combined with localized irradiation produced the longest median survival compared to either treatment alone in mice bearing orthotopic GSC-derived tumors, although the difference was not statistically significant. These findings support further clinical investigation to validate these preclinical findings and determine the potential role of FGFR inhibition as part of multimodal GBM therapy. Full article

Background: Spinal solitary fibrous tumors (SFTs) are a rare oncological entity, almost anecdotal in the pediatric population. They have a high relapse rate and represent an ongoing oncological challenge. Methods: In this article, we conducted a systematic review starting from a case report to highlight the current state of the art in managing these tumors. Results: Spinal solitary fibrous tumors (SFTs) are rare, slow-growing neoplasms that can be either intra- or extramedullary. Only a limited number of studies focus on primary pediatric spinal cord localization. Five pediatric cases of spinal SFT have been documented in the literature. On MRI, they typically present as highly vascularized, contrast-enhancing masses. Histologically, they are composed of spindle-shaped cells within a collagenous stroma featuring staghorn-shaped blood vessels. More aggressive subtypes, such as dedifferentiated SFTs, resemble high-grade sarcomas. The NAB2–STAT6 fusion is a key marker, driving EGFR signaling, collagen production, and fibrosis. Additional diagnostic markers include CD34, CD99, and Bcl-2. Surgical resection remains the primary treatment. In metastatic cases, chemotherapy—mainly with anthracyclines, dacarbazine, or temozolomide—is employed, although no standardized pediatric protocols exist. Anti-angiogenic agents, including tyrosine kinase inhibitors, have shown promise. Radiotherapy is used postoperatively for local disease control, but its impact on survival is still under investigation. Conclusions: Surgery remains the cornerstone of treatment, significantly impacting the natural history of the disease and symptom control. While clinical trials exploring radiotherapy and chemotherapy are ongoing in adults, no specific treatment protocol has been established for pediatric patients. Full article