Melanoma, a highly aggressive skin cancer, is characterized by its strong metastatic potential and resistance to standard treatments. Recent cancer research has emphasized the significance of exosomes, a type of extracellular vesicle and particle, in mediating cell-to-cell communication and driving tumor progression. Melanoma-derived exosomes contribute to metastasis by facilitating immune evasion, modulating the tumor microenvironment, and inducing epithelial-to-mesenchymal transition. The exosomal cargos, including nucleic acids (DNA, microRNA, long noncoding RNA, and circular RNA), proteins, lipids, and other biomolecules, play critical roles in reprogramming recipient cells to support tumor growth and spread. These exosomes also aid in forming pre-metastatic niches by transferring pro-inflammatory cytokines, extracellular matrix remodeling enzymes, and angiogenic factors to distant organs, preparing these sites for tumor colonization. Furthermore, tumor-derived exosomes promote therapy resistance by delivering drug-resistant molecular signatures, which diminish treatment efficacy. This emerging evidence highlights the therapeutic potential of exosomebased strategies, including inhibitors of exosome biogenesis and uptake or the use of engineered exosomes for targeted drug delivery. Advances in precision medicine also facilitate the use of exosome-derived molecular signatures in early-stage diagnosis and treatment monitoring through liquid biopsy. However, clinical translation remains challenging due to cargo heterogeneity, lack of standardized isolation methods, and potential off-target effects in exosome-based therapies. Addressing these challenges could lead to more effective therapies and better patient outcomes. This review synthesizes current knowledge on the biogenesis, composition, and functional roles of tumor-derived exosomes in metastasis, alongside their potential applications as biomarkers and therapeutic strategies. Deciphering exosomal dynamics in melanoma may open new avenues for advanced diagnostics and treatments.

Glioblastoma (GBM) is the most common and aggressive primary central nervous system malignancy. Significant resistance to therapeutic intervention is a core feature of GBM that drives tumor recurrence and underlies the remarkably poor clinical outcomes associated with this disease. This review explores the therapeutic strategies and molecular pathways involved in GBM. Therapy resistance in GBM depends on multiple interconnected macrostructural and biomolecular mechanisms, including aggressive and diffuse invasion, tumor microtube network formation, stem-like cell enrichment, selective neurovascular permeability, an immunosuppressive microenvironment, and a high degree of inter-and intra-tumoral heterogeneity. Collectively, these pathobiological features insulate specific tumor compartments and maintain GBM viability despite significant treatment-induced cellular stress. While there is enthusiasm for addressing GBM therapeutic resistance, the scale of the challenge remains immense. The identified resistance mechanisms extensively interact and can compensate for single-target assaults. Emerging overlaps between neuro-oncology and developmental neurobiology additionally suggest that GBM may exploit therapeutic resistance mechanisms yet to be identified, functioning beyond the current scientific understanding. Thus, the scope and diversity of this problem demand a comprehensive therapeutic approach capable of targeting multiple interacting mechanisms of therapeutic resistance.

Therapeutic resistance remains a significant challenge in cancer treatment, often resulting in relapse and poor outcomes. Conventional chemotherapies, such as cisplatin and paclitaxel, are frequently undermined by the development of chemoresistance and systemic toxicity. Targeted therapies, such as receptor tyrosine kinase (RTKs) inhibitors and monoclonal antibodies (mAbs), offer better specificity but face resistance over time. Combination therapies are being explored to improve efficacy and mitigate resistance. Honokiol, a biphenolic natural compound derived from Magnolia species, has emerged as a potential adjunct in combination therapies due to its anti-cancer, anti-inflammatory, and immunomodulatory properties. It enhances the efficacy of chemotherapies, such as cisplatin and paclitaxel, RTK inhibitors, such as cabozantinib and erlotinib, and mAbs, such as cetuximab. Notably, honokiol combined with mAbs has shown promise in pre-clinical studies by reactivating the immune system and reducing tumor growth in resistant models. In addition, honokiol aids in post-transplant cancer prevention by modulating immune responses, reducing tumor progression, and lowering the required dose of immunosuppressants, such as cyclosporine A and rapamycin. Pre-clinical studies in renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC), and non-small cell lung cancer emphasize its potential to overcome resistance. Despite promising evidence, further clinical studies are needed to validate honokiol as a viable adjunct in combination therapies. While several reviews have focused on the effects of honokiol alone, there is a lack of comprehensive studies examining its potential in combination with other therapies. This review aims to fill this gap by offering critical insights into the role of honokiol as a candidate for combination therapy.

Glioblastoma multiforme (GBM) is an aggressive and lethal brain tumor with limited treatment options and poor prognosis. Standard therapies such as surgery, radiation, and chemotherapy provide modest survival benefits but are often ineffective against tumor recurrence. Tumor treating fields (TTF) therapy has emerged as a promising non-invasive treatment modality that uses alternating electric fields to disrupt cancer cell division and inhibit tumor growth. However, the optimization and practical implementation of TTF systems remain challenging due to limitations in field penetration, electrode design, and treatment efficacy. In this study, we designed and developed a novel TTF prototype system to enhance electric field transmission and optimize therapeutic efficiency. The system incorporates high-dielectric ceramic electrodes made of barium titanate zirconate, allowing for superior field penetration. We evaluated the system through a series of in vitro and in vivo experiments. In vitro, GBM cells exposed to the TTF system exhibited significant reductions in proliferation, with higher field intensities yielding greater inhibition. In vivo, using a rat GBM model, we observed marked tumor suppression, as validated by bioluminescence imaging and magnetic resonance imaging. Survival analysis further demonstrated prolonged lifespan in TTF-treated rats compared to controls. Our findings highlight the potential of this novel TTF system to improve GBM treatment outcomes. This study provides a comprehensive framework for future advancements in TTF therapy, paving the way for clinical translation and further integration with conventional and emerging cancer therapies.

Drug resistance and poor prognosis in hepatocellular carcinoma (HCC) underscore the urgent need for novel treatments. Disulfidptosis, a recently identified form of metabolism-related regulated cell death, plays a complex role in anti-tumor immunity; however, its precise function in HCC remains unclear. Understanding the proteins and pathways involved in disulfidptosis and its association with disulfidptosisrelated genes (DRGs) in HCC could reveal innovative therapeutic strategies. This study employs bioinformatics to examine the correlation between DRGs and both clinical prognosis and immune status in HCC patients. Risk models were constructed using univariate Cox and least absolute shrinkage and selection operator regression to identify significant genes, with risk scores correlated to survival outcomes across various patient subtypes. In addition, the analysis explored the association of DRGs with prognosis, immune cell infiltration, enriched functional pathways, and immune checkpoints. The risk model identified six key genes: FLNA, NCKAP1, CD2AP, RPN1, SLC7A11, and CAPKAP. Validation through the receiver operating characteristic curve demonstrated the model's exceptional predictive power. Gene network analysis revealed ten essential genes, three of which (FLNA, CD2AP, and CAPZB) were shared with the risk model. FLNA and CAPZB have previously been linked to therapeutic indicators and pathways in HCC. However, there is a lack of comprehensive data connecting CD2AP to clinical therapy or HCC pathways. These findings highlight the significance of DRGs in HCC prognosis and immune regulation, suggesting that DRGtargeted therapies may offer new avenues for HCC treatment.

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide, with genetic factors playing a significant role in its pathogenesis. This study investigated the prevalence of two single-nucleotide polymorphisms (SNPs) -rs9929218 in the Cadherin 1 (CDH1) gene and rs6983267 in the 8q24 region among Kurdish CRC patients in Sulaymaniyah, Iraq, and assessed their association with clinicopathological features. Blood samples from 290 CRC patients and 100 healthy controls were analyzed using allele-specific polymerase chain reaction. The frequency of rs9929218 was 20.34% in CRC patients compared to 70% in controls, while rs6983267 was detected in 26.55% of CRC cases versus 11% of controls. Both SNPs were significantly associated with CRC risk in univariate analyses; however, after adjusting for age, sex, tumor grade, and TNM stage in multivariate logistic regression, neither SNP remained an independent risk factor. Nonetheless, both SNPs showed significant associations with advanced tumor stage, nodal involvement, and perineural invasion, suggesting a potential role in disease progression rather than initiation. These findings enhance the understanding of CRC genetics in the Kurdish population and highlight the need for larger, functionally validated studies to confirm these associations.

Just like us, cells communicate, but in their own unique way. Using waves as their common language, cells signal to each other about where and when to move. They talk, share information, and collaborate. The human body comprises trillions of cells that continuously adapt to their surroundings, exchanging millions of vital signals for survival. This communication must be meticulously regulated, as any disruption can lead to errors, such as the abnormal cell growth observed in cancer. The interaction between cancer cells and their neighboring cells is bidirectional, involving a complex network of mechanisms that can drive aggressive tumor behaviors-such as rapid growth, spread, and treatment resistance-or, conversely, act to suppress malignancy. This dynamic interplay within the tumor microenvironment unfolds through two primary modes: direct communication through physical cell contact, mediated by adhesion molecules, electrical signals, or the exchange of materials through gap junctions, and indirect communication facilitated by paracrine signaling. The latter involves the release of signaling molecules like cytokines, growth factors, and extracellular vesicles. Disrupting these cellular dialogues presents a promising therapeutic frontier. Specifically, strategies that integrate interventions targeting tumor communication pathways with conventional chemotherapy could enhance treatment efficacy, offering a synergistic approach to hinder cancer progression and improve outcomes. This article delves into the role of cell-to-cell communication in cancer development, its impact on metastasis, and how ongoing research is broadening our understanding of the disease.

Diffuse large B-cell lymphoma (DLBCL) in the splenic hilar lymph node mimicking an intrasplenic lesion is considered rare in the literature. This case is discussed as a form of a primary splenic DLBCL and as a stage I/II abdominal DLBCL. Primary splenic DLBCL was previously defined as a lymphoma confined to the spleen, with or without involvement of the hilar lymph node or distant lesions. However, the condition is not included in the 5^th edition of the World Health Organization classification. In this report, we describe the case of a 63-year-old Japanese male who presented with a 5 cm ¹⁸F-fluorodeoxyglucose-avid mass identified on imaging, presumed to be an intrasplenic mass. Subsequent splenectomy confirmed that the mass was DLBCL originating from the splenic hilar lymph node, distinctly separated from the spleen and the tail of the pancreas. Postoperatively, the patient responded well to treatment comprising three courses of a combined regimen of polatuzumab vedotin, rituximab, cyclophosphamide, daunorubicin, and prednisolone. This case underscores the importance of caution when diagnosing intrasplenic lesions based on imaging, as the lesions may be located outside the spleen.

Desmoplastic small round cell tumors are extremely rare, occurring primarily in young males. This disease is characterized by the reciprocal translocation of the EWS-WT1 fusion gene. Treatment for this tumor is multidisciplinary, including surgery, chemotherapy, and radiation therapy. The disease progresses rapidly and even with complete resection, local recurrence, and distant metastasis is likely to occur and the prognosis is poor. This report describes a case of primary ovarian cancer in a 33-year-old woman. The pre-operative test showed elevated CA125, CA19-9 and carcinoembryonic antigen, and hypercalcemia. Staging laparotomy was performed without residual tumor. The clinical stage was IIB, and adjuvant chemotherapy was performed. Immediately after the end of chemotherapy, multiple lymph node metastases, and the patient subsequently experienced repeated recurrences and died 10 months after surgery. In the future, it is desirable to establish standard treatment for desmoplastic small round cell tumors by analyzing more cases.