Search Results (38,628)

Antibody–drug conjugates (ADCs) are a rapidly evolving class of oncology therapeutics that enable precise delivery of potent cytotoxic agents to tumor cells while minimizing systemic toxicity. While HER2-targeted ADCs such as trastuzumab deruxtecan (T-DXd) in HER2-mutant, Datopotamab deruxtecan (Dato-Dxd) in EGFR-mutant, and telisotumumab vedotin (Teliso-V) in MET IHC 3+ expressing lung cancer have already established a clinical role in non-small cell lung cancer (NSCLC), multiple ADCs targeting alternative antigens, including additional TROP2 ADCs, HER3, MET, CEACAM5, B7-H3, Nectin-4, and others, are now in advanced clinical development. This review synthesizes the current evidence for non-HER2 ADCs in NSCLC, highlighting mechanisms of action, clinical efficacy, safety profiles, biomarker strategies, and emerging resistance mechanisms. Key safety concerns, including interstitial lung disease (ILD), ocular toxicity, and peripheral neuropathy, are emphasized alongside approaches for re-challenge following toxicity. We further discuss next-generation ADC platforms, including bispecific and conditionally activated constructs, as well as combination strategies with immunotherapy. Collectively, ADCs beyond HER2 are poised to reshape treatment paradigms in NSCLC, offering hope for patients with limited therapeutic options. This review identifies current gaps, highlights ongoing research priorities, and proposes practical considerations for integrating these therapies into clinical practice. Full article

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality and is characterized by substantial molecular heterogeneity, including epigenetic dysregulation. Histone acetylation, regulated by histone acetyltransferases and histone deacetylases (HDAC), has been implicated in CRC development and progression. The aim of the present study was to evaluate HDAC-2 expression in CRC and investigate its association with clinicopathological parameters and patient outcomes. Methods: In this retrospective study, tumor tissue samples from 77 patients with CRC and documented recurrence were examined. HDAC-2 expression was assessed by immunohistochemistry and classified as low or high using a semi-quantitative scoring system. Associations with clinicopathological parameters and survival outcomes (disease-free survival, DFS; overall survival, OS) were analyzed. Results: High HDAC-2 expression was associated with younger patient age and earlier disease recurrence, while its association with overall survival was borderline. Conclusions: HDAC-2 expression may have clinicopathological relevance in CRC, particularly in relation to recurrence-related outcomes, although larger studies are needed to confirm its prognostic significance. Full article

Vogt–Koyanagi–Harada syndrome (VKH) is a rare granulomatous autoimmune disease characterised by a systemic immune response directed against melanocytes. This multisystem condition primarily affects organs that are rich in melanocytes, such as the eyes, inner ear, meninges and skin. VKH might be responsible for the development of chronic uveitis and permanent visual impairment, particularly in cases where a diagnosis is delayed and treatment is not administered in a timely manner. A key factor in its pathogenesis is the loss of immune tolerance to melanocytes, driven by a T-cell–mediated immune response and genetic susceptibility, including the presence of HLA-DRB1*04 antigens. In recent years, immune checkpoint inhibitors (ICIs) have become the standard treatment in oncology, including non-small cell lung cancer and unresectable melanoma. However, it should be noted that their utilisation carries with it the potential for immune-related adverse events, including rare cases of VKH-like uveitis. The objective of this review is to outline the clinical features of VKH syndrome, examine current diagnostic and treatment approaches, and emphasise the immunopathological mechanisms associated with drug-induced forms of VKH, with a particular focus on programmed cell death protein 1 (PD-1) inhibitors. The article also includes an analysis of the genetic, epigenetic, and environmental factors that predispose individuals to the disease. This analysis facilitates a deeper understanding of the pathogenesis of the disease and assists in the identification of patients at increased risk of drug-induced VKH manifestations. Full article

Bone metastasis remains a major cause of morbidity in advanced cancer, driven not only by tumor–bone crosstalk but also by profound immune remodeling within the marrow. Myeloid-derived suppressor cells (MDSCs), including polymorphonuclear (PMN-MDSC) and monocytic (M-MDSC) subsets, are increasingly recognized as central effectors of this process, integrating inflammatory signals with metabolic and stromal cues to enforce immune suppression and support skeletal colonization. In this review, we synthesize current evidence that bone metastases transform the bone marrow into an “MDSC amplifier,” where vascular and endosteal niches, CXCL12-rich stromal compartments, hypoxia, and adipocyte-derived lipids collectively promote MDSC recruitment, persistence, and functional maturation. We discuss the dominant suppressive programs deployed by MDSCs in bone (e.g., arginase-1 activity, reactive oxygen/nitrogen species, and checkpoint ligand expression), and how these mechanisms converge to impair cytotoxic T-cell and NK-cell responses while fostering regulatory T-cell dominance. Importantly, because the marrow is a hematopoietic organ, bone lesions can also generate systemic consequences through myeloid spillover, providing a mechanistic basis for reduced responsiveness to immune checkpoint blockade in bone-dominant disease. We then evaluate pharmacologic strategies to target MDSCs in the context of bone metastasis, including approaches that block trafficking (e.g., CCR2/CXCR2 axes), deplete or reprogram suppressive myeloid states (e.g., STAT3-directed strategies, differentiation therapy), and disrupt bone-resorptive feedback loops (e.g., receptor activator of NF-κB ligand (RANKL) inhibition and bisphosphonates), emphasizing rational combinations and sequencing to limit marrow toxicity. Finally, we highlight emerging single-cell and spatial profiling tools that can resolve bone-specific heterogeneity in MDSCs and guide biomarker-driven, mechanism-informed therapeutic development. Full article

Formaldehyde (HCHO) is a typical volatile organic compound (VOC) that poses significant risks to human health. Long-term exposure, even at low concentrations, has been associated with various malignant diseases, including nasopharyngeal, colon, and brain cancers. Common technologies for HCHO abatement include ventilation, adsorption, photocatalysis, and catalytic oxidation. Among these methods, catalytic oxidation is regarded as the most promising due to its high removal efficiency, low cost, minimal energy consumption, and no toxic by-products. In recent years, supported catalysts with excellent room-temperature activity and high dispersibility have attracted considerable attention. These catalysts can usually be divided into two categories: noble metal catalysts and non-noble metal catalysts. Zirconia (ZrO₂) has become an ideal support owing to its advantages of high specific surface area, abundant and tunable acid–base sites, and strong metal–support interaction (SMSI). Various modification strategies have been developed to improve the catalytic performance of ZrO₂-based systems, such as the construction of phase interfaces and the stabilization of single-atom species. This review summarizes the recent research progress of ZrO₂-based systems for the catalytic oxidation of formaldehyde. It provides a detailed discussion of the physicochemical properties of ZrO₂ supports and the reaction mechanisms involved, and highlights achievements in crystal phase regulation, elemental doping, metal–support interaction, and composite modification. Finally, future challenges and development directions for these catalysts are also outlined. Full article

The rising incidence of skin cancer necessitates scalable and accurate diagnostic tools. While dermoscopy-based systems have achieved expert-level performance, clinical smartphone images pose challenges due to variability in lighting, resolution, and artifacts. Recent advances in multimodal deep learning have shown promise, yet most approaches rely on simple feature concatenation or single-model classifiers, limiting their ability to capture complex cross-modal interactions. This study aims to bridge the diagnostic gap in resource-limited settings by developing a robust multimodal framework that synergizes clinical smartphone images with structured patient metadata for automated skin cancer classification. We propose a novel hybrid architecture integrating a Swin Transformer V2 (SwinV2-Tiny) for hierarchical visual feature extraction and a Denoising Autoencoder (DAE) with PCA for robust metadata embedding. These heterogeneous modalities are fused via a Gated Attention Mechanism that dynamically weighs feature importance across streams. Classification is performed by a Heterogeneous Meta-Stack Ensemble comprising CatBoost, LightGBM, XGBoost, and Logistic Regression, designed to maximize calibration and generalization across imbalanced classes. Evaluated on the PAD-UFES-20 dataset (2298 clinical smartphone images, six diagnostic classes), the proposed framework achieves state-of-the-art performance with a macro-averaged F1-score of 0.977, accuracy of 0.978, and an AUC of 0.990. It significantly outperforms unimodal baselines and existing multimodal methods, demonstrating superior sensitivity (0.974) and precision (0.981), particularly for underrepresented malignant classes like Melanoma (F1: 0.995) and Squamous Cell Carcinoma (F1: 0.960). The integration of clinical metadata with advanced visual embeddings via gated attention significantly enhances diagnostic reliability. Comprehensive ablation studies confirm the contribution of each architectural component. This framework offers a viable pathway for deploying high-precision, AI-driven dermatological screening tools on standard smartphone devices. Full article

Background/Objectives: Pediatric cancers are disorders of dysregulated development driven largely by genomic and epigenetic alterations. Precisely modeling these developmental differences is essential for understanding the unique biology of childhood cancers. Patient-derived organoids (PDOs) offer a powerful in vitro platform that recapitulates tumor heterogeneity, plasticity, microenvironment (including immune cells) and disease-relevant features. Methods: Here, we describe a step-by-step protocol for the establishment of PDOs from cells derived from pediatric brain tumors and extracranial solid tumor biopsies and bone marrow aspirates, including tumor processing, organoid culture/subculture, and cryopreservation. Results: Furthermore, we present the use of PDOs for further experimental analysis such as fluorescence imaging, Western blotting, flow cytometry, and immunohistochemistry (IHC) to investigate the underlying pathophysiology of tumorigenesis. Conclusions: Expanding the application of organoids to childhood malignancies holds exceptional promise for elucidating pediatric tumor biology and advancing therapeutic strategies, representing the long-overdue convergence of technology and clinical need. Full article

Background/Objectives: Advanced prostate cancer (PCa) evolves through adaptive mechanisms that sustain tumor growth despite the suppression of androgen receptor (AR) signaling. Accumulating evidence identifies activation of the hepatocyte growth factor (HGF)/MET pathway as a potential driver of PCa progression in advanced disease states characterized by AR-independence and therapeutic resistance. We review the biological and clinical evidence supporting MET as a context-dependent therapeutic target and discuss its implications for patient selection and combination strategies. Methods: A comprehensive narrative review of preclinical, translational, and clinical studies evaluating MET-directed therapies for PCa was performed. Results: Aberrant activation of the HGF–MET axis is frequently driven by autonomous paracrine and autocrine loops that sustain pathway activation during disease progression. MET overexpression is associated with adverse pathological features, increased tumor aggressiveness, bone metastasis, lineage plasticity, and resistance to AR-targeted treatments. Preclinical studies have demonstrated that AR suppression, tumor hypoxia and tumor–microenvironment interactions promote MET upregulation, supporting AR-independent growth and epithelial-to-mesenchymal transition. Clinical trials of MET inhibitors have shown modest activity as monotherapies, with the most consistent biological effects observed in bone-dominant disease. Recent studies indicate greater therapeutic potential when MET inhibition is incorporated into rational combination strategies targeting complementary molecular pathways. Emerging data further indicate that MET activation characterizes a biologically aggressive, AR-low or neuroendocrine-like disease state. These findings support a transition from empiric use of MET inhibitors toward precision, context-driven therapeutic development. Conclusions: MET is not a universal therapeutic target but defines a clinically relevant subset of aggressive, AR-indifferent PCa. Future development should focus on biomarker-guided patient selection and rational combination strategies. Integration of molecular profiling, imaging, and liquid biopsy approaches will be essential to identify patients most likely to benefit from MET-directed interventions. Full article

Purpose: Oral squamous cell carcinoma (OSCC) carries a substantial burden in low- and middle-income countries as well as underserved subpopulations within high-income settings, where structural barriers contribute to worse outcomes. While evidence supports targeted screening of high-risk groups, practical guidance for designing organized, quality-assured programs remains limited. This review proposes a framework to translate contemporary cancer-screening principles into operational criteria for OSCC. Methods: A review following the Scale for the Assessment of Narrative Review Articles principles was conducted. Conceptual papers, international evaluations, implementation studies, and programmatic guidance were included. The evidence was synthesized narratively, with emphasis on contemporary cancer-screening principles, implementation frameworks, and their applicability to OSCC. Results: Clinical oral examination can improve the detection of OSCC in early stages and reduce mortality among high-risk groups when embedded in coordinated care pathways. Effective programs require governance structures, screening policies, risk-stratified approaches, and robust information systems capable of call-recall, referral tracking, and quality monitoring. Dental schools and academic clinics may serve as feasible regional hubs for programs within mixed health systems. Conclusions: Aligning core OSCC-screening principles with operational enablers offers a practical pathway to develop context-appropriate programs that strengthen capacity, promote equity, and generate evidence for responsible scale-up. Full article

The Hippo, as a central pathway regulating cell proliferation, apoptosis, stem cell homeostasis and organ development, is closely associated with the onset and progression of tumors, metabolic reprogramming, drug resistance and immune evasion when it is abnormally inactivated. The Hippo not only directly promotes tumor cell proliferation, maintains cancer stem cell properties, and mediates metabolic reprogramming and treatment resistance, but also reshapes the tumor microenvironment(TME) by regulating the formation, heterogeneity and function of cancer-associated fibroblasts (CAFs). Furthermore, it mediates tumor immunosuppression and immune evasion by modulating programmed death-ligand 1(PD-L1) expression, T-cell function, macrophage polarization and cytokine secretion. At the same time, inflammatory cytokines, growth factors, metabolites and physical signals within the TME can negatively regulate the activity of the Hippo, creating a pro-tumor positive feedback loop. This article provides a systematic review of the composition and regulation of the Hippo , its mechanisms of action in the biological behavior of tumor cells and interactions within the tumor microenvironment, as well as progress in the development of drugs targeting this pathway. It offers a theoretical basis for a deeper understanding of the role of the Hippo in tumors and for the development of novel anti-tumor therapeutic strategies. Full article

Background: Gliomas are the most common malignant brain tumors in adults, characterized by a poor prognosis. Although the current World Health Organization (WHO) classification provides clear guidelines for classifying oligodendroglioma, astrocytoma, and glioblastoma patients, significant heterogeneity persists within each class, limiting the effectiveness of current treatment strategies. With the increasing availability of large-scale multi-omics datasets resulting from advancements in sequencing technologies and online repositories that provide them, such as The Cancer Genome Atlas (TCGA), it is now possible to investigate these tumors at multiple molecular levels. Methods: In this work, we apply integrative multi-omics analysis to explore the interplay between genomic (mutations), epigenomic (DNA methylation), and transcriptomic (mRNA and miRNA) layers. Our approach relies on Multi-Omics Factor Analysis (MOFA), a Bayesian latent factor analysis model designed to capture sources of variation across different omics types. Results: Our results highlight distinct molecular profiles across the three glioma types and identify potential relationships between methylation and genetic expression. In particular, we uncover novel candidate biomarkers associated with survival as well as a transcriptional profile associated with neural system development. Conclusions: These findings may contribute to more personalized therapeutic strategies, potentially improving treatment effectiveness and survival outcomes in this disease. Full article

Liver cancer remains a significant global health burden, requiring the development of precise nucleic acid delivery systems. Lipid nanoparticles (LNPs) are leading candidates; however, their efficiency is governed by the pK_a of ionizable lipids, which dictates nanoparticle stability and endosomal escape. In this study, we employed a machine learning–driven quantitative structure–activity relationship framework to predict the pK_a of ionizable lipids derived from the DLin–KC2–DMA scaffold. Utilizing a dataset of 56 compounds, we compared Random Forest, Artificial Neural Network, and Extreme Gradient Boosting (XGB) models integrated with Permutation Importance (PI) for feature selection. The optimized PI–XGB model exhibited exceptional predictive accuracy (R² = 0.970, R²_CV = 0.901, RMSE_test = 0.115) and robust generalization confirmed via external validation (RMSE_ext. = 0.313). Mechanistic insights derived from SHapley Additive exPlanation analysis identified charge distribution, molecular topology, and polarity as critical determinants of lipid ionization. These results demonstrate the power of interpretable machine learning in elucidating molecular structure–property relationships, offering a robust computational strategy for the rational design of next–generation ionizable lipids to optimize LNP–mediated gene therapy for liver cancer. Full article

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality despite major advances in diagnostics and therapies. The prognosis remains poor, mostly due to late-stage presentation and molecular heterogeneity. Epidermal growth factor receptor (EGFR) mutations are common drivers of NSCLC. The development of EGFR tyrosine kinase inhibitors (TKIs) has significantly improved outcomes in patients with EGFR mutations. Variant allele frequency (VAF) is a quantitative genomic measure representing the proportion of sequencing reads harboring a given mutation. In NSCLC tissue, the EGFR mutation VAF reflects tumor clonality and intratumoral heterogeneity, and accumulating evidence suggests an association between EGFR VAF and response to EGFR-targeted TKIs. Methods: To address the limited synthesis of data on the relevance of EGFR mutation VAF in NSCLC, we conducted a narrative review of the literature using PubMed/MEDLINE and Embase databases and current clinical guidelines, synthesizing available evidence on EGFR VAF, including its biological, molecular, and therapeutic implications in EGFR-mutated disease. The review was structured in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) checklist. Results: EGFR VAF and on-treatment VAF dynamics are consistently associated with treatment response, progression-free survival, and overall survival in osimertinib-treated NSCLC. Baseline VAF enables risk stratification, early clearance kinetics predict durable benefit, and longitudinal VAF monitoring facilitates early detection of resistance. Importantly, the prognostic implications of VAF differ fundamentally between tissue-based and plasma-based measurements: high tissue VAF reflects clonal homogeneity and predicts favorable TKI response, whereas high plasma VAF indicates elevated tumor burden and is associated with inferior outcomes. In the second-line setting, the T790M/activating mutation ratio serves as a surrogate for resistance clonality and independently predicts osimertinib efficacy. Conclusions: EGFR VAF represents a promising dynamic molecular biomarker for treatment monitoring and precision decision-making in EGFR-mutated NSCLC. Full article

DNA methylation is a fundamental epigenetic modification that regulates gene expression, genome stability, and cell identity across vertebrate development. Disruption of DNA methylation homeostasis contributes to a wide spectrum of human diseases, including developmental disorders, neurological conditions, and cancer. Understanding how DNA methylation patterns are established, maintained, and dynamically remodeled during development is therefore essential for elucidating disease mechanisms and identifying therapeutic opportunities. The zebrafish (Danio rerio) has emerged as a powerful vertebrate model for investigating DNA methylation dynamics in vivo. Its external fertilization, optical transparency, rapid embryogenesis, and high fecundity enable direct observation and experimental manipulation of epigenetic processes at developmental stages that are difficult to access in mammalian systems. In addition, the core enzymatic machinery governing DNA methylation, including DNA methyltransferase (DNMT) and ten-eleven translocation (TET) protein families, is evolutionarily conserved between zebrafish and humans. In this review, we summarize current knowledge of the zebrafish methylome and the enzymatic regulators that control DNA methylation dynamics. We discuss how DNA methylation shapes early embryonic development, organogenesis, and cell fate decisions, and highlight insights gained from zebrafish models of human disease. Finally, we examine emerging technologies that are enabling increasingly precise interrogation of epigenetic regulation in vivo. Together, these advances position zebrafish as an important platform for bridging developmental epigenetics with human disease biology and therapeutic discovery. Full article

Background/Objectives: The androgen receptor (AR)-driven transcriptional program plays a pivotal role in the development and progression of prostate cancer. The binding of androgen dihydrotestosterone (DHT) to AR initiates transcriptional activation, thereby altering the transcriptional landscape. DHT-induced long non-coding RNAs (lncRNAs) have been recognized as crucial players in prostate cancer pathogenesis. This study aims to identify and explore the important role of such lncRNAs in prostate cancer. Methods: This study first analyzed transcriptome data from an androgen-dependent cell line, LNCaP, treated with different DHT concentrations and found a batch of lncRNAs exhibiting DHT concentration dependence. TCGA data suggested a correlation between the DHT-induced lncRNA and prostate cancer. Finally, a series of in vivo and in vitro experiments confirmed the effect and mechanism of lncRNA in prostate cancer. Results: AC092718.4 was highly expressed in AR-positive prostate cancer cell lines and tissues, and its expression in patients with Gleason scores 6–9 was significantly higher than in a normal control group. Notably, the expression level of AC092718.4 was upregulated in a concentration-dependent manner with DHT. In vitro experiments revealed that overexpression of AC092718.4 promoted cell proliferation and inhibited cell apoptosis. Conversely, knockdown of AC092718.4 suppressed tumorigenesis in vivo. Furthermore, our investigation into the pathogenetic mechanism demonstrated that AC092718.4 could act as an miRNA sponge for miR-138-5p, attenuating its inhibitory effect on downstream oncogenes, such as FERMT2, RHOC, and HIF1A. These AC092718.4/miR-138-5p/mRNA axes, in turn, facilitated the progression of prostate cancer. Conclusions: For the first time, we demonstrate that AC092718.4 may function as an oncogenic factor in prostate cancer. The AC0927.8.4/miR-138-5p/mRNA axes potentially offer promising diagnostic and therapeutic targets for prostate cancer. Full article