PAX3 plays a vital role in regulating proper growth, migration, differentiation, and survival during development of normal tissues, including those derived from the embryonic neural crest. PAX3 is a transcription factor with two separate DNA-binding domains and can positively (and less frequently, negatively) regulate gene expression. The levels of PAX3 can be modified by upstream molecular pathways, and its subsequent downstream functions are regulated through a wide range of protein interactions and posttranscriptional modifications. PAX3 direct downstream target genes are other transcription regulators and factors that modulate cellular proliferation, lineage specificity, migration, and survival. The pathways that PAX3 regulates during development may be recycled and subverted during disease progression, for example, during cancer progression, growth, and metastasis. Indeed, PAX3 is overexpressed in several cancers, including melanoma, neuroblastoma, and rhabdomyosarcoma. While there is still much that is unknown about the mechanisms by which PAX3 controls such a wide array of key cellular functions, a great deal of progress has been made to advance our understanding of this critical and multi-faceted factor.

Xeroderma pigmentosum group B (XPB/ERCC3) and group D (XPD/ERCC2) helicases are integral components of the transcription factor IIH (TFIIH) complex, coordinating DNA unwinding during transcription initiation and nucleotide excision repair (NER). XPB functions as an ATP-driven translocase that generates torsional strain to promote promoter melting and DNA opening at lesion sites, whereas XPD acts as a 5' to 3' helicase responsible for lesion verification and extension of the repair bubble. Structural and biochemical studies have clarified how TFIIH subunits regulate these helicases-p52 and p8 modulate XPB's translocation activity, while p44, p62, and MAT1 control XPD's helicase function through conformational and compositional transitions within the complex. Beyond their canonical roles, XPB and XPD participate in diverse cellular pathways, including cell-cycle regulation and oxidative stress response, highlighting their involvement in maintaining genome integrity beyond repair and transcription. Mutations in either helicase lead to xeroderma pigmentosum (XP), trichothiodystrophy (TTD), or combined XP/Cockayne syndrome (XP/CS) phenotypes, emphasizing the essential role of TFIIH integrity for human health. Recent biochemical and pharmacological advances have further revealed the therapeutic relevance of these helicases-XPB as a target of small-molecule inhibitors such as triptolide, Minnelide, and spironolactone, and XPD as a potential modulator of cancer sensitivity to DNA-damaging treatments. Collectively, XPB and XPD exemplify the structural and functional versatility of TFIIH helicases across repair, transcription, and genome maintenance.

Gene therapy has emerged as a promising therapeutic strategy in oncology by targeting the molecular mechanisms that drive malignant transformation. Among gene-based approaches, oncolytic viruses (OVs) are distinctive in their ability to selectively replicate within tumor cells, induce direct oncolysis, and simultaneously stimulate systemic antitumor immunity by exploiting defects in cancer cell antiviral responses. Recent studies have identified Coxsackievirus A11 (CVA11) as a highly potent immunostimulatory OV. CVA11 demonstrates strong tumor-selective replication, robust cytolytic activity, and marked induction of antitumor immune responses. Notably, CVA11 has been shown to induce complete tumor regression in human non-small cell lung cancer models. In addition, CVA11 enhances chemosensitivity in oxaliplatin-resistant colorectal cancer and may have broader applicability in treatment-refractory malignancies, including pancreatic cancer. This review summarizes current gene therapy strategies for malignant tumors with a particular focus on the biological properties and therapeutic potential of CVA11. We discuss its mechanisms of tumor selectivity, immune activation, and potential integration with chemotherapy and gene-based cancer vaccines. Collectively, these findings position CVA11 as a promising next-generation oncolytic virus for cancer gene therapy and immunotherapy.

Acute myeloid leukemia (AML) is a lethal and rapidly progressive hematologic malignancy with high rates of relapse and treatment refractoriness. Management of AML is complicated by biological heterogeneity in a disease that is broadly defined by the clonal expansion of myeloblasts that otherwise play an important role in healthy marrow tissues. While subtypes of AML are increasingly defined by druggable driver mutations including FLT3-ITD, IDH1, IDH2, and NPM1, conventional chemotherapy and reduced intensity induction regimens (e.g., azacitidine-venetoclax) remain therapeutic backbones. One area of active development for personalization of AML treatment is the assessment of measurable residual disease (MRD). MRD testing in AML is complicated by uncertainty regarding the physiologic compartment of persistent and relapsing myeloblasts, and by increasing recognition of myeloid driver mutations in some healthy bone marrow states, such as clonal hematopoiesis of indeterminate potential (CHIP). Even in large academic centers, MRD tools are not yet universally available. Standardized workflows for MRD implementation are only beginning to enter consensus and guideline documents. Current understanding of AML biology and state-of-the-art tools for MRD measurement are reviewed here in an effort to promote clinical and laboratory investigator collaboration for the development of reliable tools for improving outcomes in this deadly disease. Clinical trial number: not applicable.

Measurable residual disease (MRD) has become a central determinant of prognosis and treatment planning in acute myeloid leukemia (AML). MRD assessment is now aided by a wide range of technologies, including next-generation sequencing, PCR-based assays, multiparameter flow cytometry, and emerging approaches such as liquid biopsy platforms and imaging-based detection. These modalities differ in sensitivity, applicability, and interpretive framework, yet each offers distinct advantages in specific disease contexts. Beyond technical issues, MRD is becoming increasingly integrated into clinical practice. In non-intensive treatment settings, where targeted and low-intensity regimens rely on dynamic disease monitoring to guide ongoing management, MRD is increasingly being used to inform therapeutic decisions. In the peri-transplant setting, MRD status influences conditioning strategies, donor selection, and the use of post-transplant interventions. Despite the growing evidence supporting the clinical relevance of MRD across these scenarios, challenges remain regarding standardization, optimal timing of assessment, and the interpretation of discordant results. This review summarizes the full landscape of MRD detection methods and examines the evolving role of MRD in contemporary AML management, emphasizing current applications and areas requiring further refinement.

Gastric cancer (GC) remains a major global health burden, with its unfavorable prognosis primarily driven by extensive tumor heterogeneity. Traditional bulk omics, while informative, are inherently limited by the averaging effect of diverse cell populations and fail to capture the critical spatial molecular disparities within the tumor and its microenvironment (TME). Single-cell omics can capture cellular heterogeneity but lack spatial context. Therefore, there is an urgent clinical need for spatial multi-omics to provide a high-definition dissection of GC heterogeneity and to optimize therapeutic efficacy. This review first outlines briefly the evolution of spatial technologies, including transcriptomics, proteomics, metabolomics, genomics and epigenomics, and their transformative applications in GC research. We further explore how these platforms refine molecular classification beyond traditional models, identify next-generation biomarkers, and decode the intricate cellular interactions governing immune evasion and metastasis. Next, we highlight the pivotal role of spatial profiling in unravelling the multidimensional mechanisms of resistance to chemotherapy, targeted therapy and immunotherapy. Finally, we address current technical bottlenecks and discuss prospects for clinical translation.

Lamin A/C is emerging as a promising candidate regulator at the intersection of nuclear mechanics, chromatin organization, and gene regulation, linking structure and regulation, mechanics and epigenetics, constraint and plasticity. Lamin A/C was previously considered a static structural scaffold; however, it is now recognized as a dynamic component of nuclear organization that links physical cues to epigenetic and transcriptional states. Lamin A/C regulates three-dimensional genome structure, constrains chromatin mobility, and influences cell transitions between plastic and committed states through its interactions with heterochromatin at the nuclear periphery and active chromatin domains in the nuclear interior. In cancer, these functions appear to be dependent on the context. Lamin A/C has been implicated in crucial biological processes, including invasion, survival under mechanical stress, lineage plasticity, and therapeutic response. Its prognostic value varies across tumor types. This heterogeneity indicates that lamin A/C does not function as a traditional oncogene or oncosuppressor; instead, it operates as a nuclear rheostat, influencing the behavior and development of tumor cells. This review examines the potential clinical benefits of lamin A/C while considering its implications for normal tissue functions. It aims to improve understanding of cellular adaptability and vulnerability in cancer through the exploration of lamin A/C biology.

From an epidemiological perspective, polymorphous low-grade neuroepithelial tumor (PLNTY) represents a small proportion of brain tumors encountered in epilepsy surgery series. Their rarity and relatively recent recognition likely contribute to underdiagnosis and poor prognosis. In terms of histopathological features, they are similar to oligodendrogliomas. Molecular analyses can be used to show the fusion between fibroblast growth factor receptor (FGFR3) and transforming acidic coiled coil (TACC) proteins, which most commonly results in progression towards glioblastoma (GBM). We report a case of a 62-year-old man who underwent left frontal craniotomy to remove a frontal mass. Histologically, the glial lesion consisted of elements associated with oligodendroglia-like features. Immunohistochemistry was positive for glial fibrillary acidic protein (GFAP), oligodendrocyte transcription factor 2 (OLIG2), and α-thalassemia X-linked mental retardation syndrome (ATRX) nuclear expression, but negative for isocitrate dehydrogenase 1 (IDH1) and BRAF-V600E. Next-generation sequencing showed the FGFR-TACC3 fusion, and taken together, these findings supported the final diagnosis of PLNTY. During follow-up, the patient underwent a second neurosurgery, where histological evaluation indicated a GMB. This article presents clinical and radiological data, morphology, immunohistochemistry, molecular features, and treatment to enhance the clinical and pathological understanding of PLNTY with FGFR3-TACC3 fusion for all professionals involved in medical decisions.

KRAS-targeted therapy has opened new doors in the world of oncology, and many trials are underway for KRAS specific treatments for gastrointestinal (GI) malignancies. Outlining the current state of KRAS therapy and the remaining research gaps pertaining to these deadly cancers is crucial for the development of future therapeutics. In this review, we focus on the relationship between KRAS and GI malignancies. Current therapies are discussed with an in-depth exploration of the KRAS gene and how it connects to pancreatic, colorectal and other GI malignancies. Promising clinical trials and future therapies are highlighted while discussing the molecular biology behind them. Specifically, trials focusing on upcoming KRAS on and off inhibitors in development as well as variant focused inhibitors targeting the more common mutations G12D and G12V. We discuss exciting new pan/multi KRAS inhibitors that have been successful in pre-clinical trials. More unique therapeutic options include KRAS T cell therapies, vaccines, and combination strategies with immunotherapy. Furthermore, we address the difficulties with KRAS therapy, and the potential future directions needed to overcome them. An in-depth current literature review was done along with a review of the active clinical trials for KRAS-targeted therapeutics involving GI malignancies.

Juvenile nasopharyngeal angiofibroma (JNA), a rare vascular tumor in adolescent males, involves dysregulated angiogenesis and hormonal interplay. Key molecular drivers include HIF-1α, VEGF, bFGF, and β-catenin, promoting tumor growth via pathways like Wnt/β-catenin and Ras signaling. Androgens and estrogen modulate progression, though mechanisms remain debated. Targeted therapies reduce tumor proliferation and vascularity in preclinical studies, yet clinical translation is hindered by drug resistance and inconsistent biomarker expression. Hormonal and MMP-targeted approaches also show potential but require validation. This review consolidates JNA's molecular landscape, emphasizing the need for personalized strategies, biomarker refinement, and combination therapies to improve therapeutic outcomes for this challenging tumor.

Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a multifunctional protein belonging to the heterogeneous nuclear ribonucleoprotein family. The K‑homology domain is the most evolutionarily conserved feature of hnRNPK and is responsible for RNA‑binding. hnRNPK interacts with both chromatin and RNA in numerous species. Initially characterized as an RNA‑binding protein, hnRNPK functions as a structural protein, integrating a number of signaling pathways and participating in gene expression regulation, RNA processing, cell cycle control and apoptosis. hnRNPK exhibits aberrant expression in numerous tumors, functioning paradoxically as either an oncogene or tumor suppressor depending on cellular context, expression levels and post‑translational modifications. Recent advancements have outlined the involvement of hnRNPK in tumor cell migration, angiogenesis and chemoresistance through interactions with long non‑coding RNAs and the regulation of key signaling pathways. The present review summarizes current knowledge regarding the structure, function and clinical importance of the hnRNPK in cancer, highlighting its potential as both a biomarker and therapeutic target.

MicroRNAs (miRNAs or miRs) are a class of small non‑coding RNAs that are critical regulators of gene expression. By targeting messenger RNAs, they play essential roles in various biological processes, including development, differentiation, immunity, metabolism and apoptosis. miRNA dysregulation is often associated with tumorigenesis and cancer progression. miR‑124, a miRNA predominantly and specifically expressed in the central nervous system, is commonly downregulated in various cancers. It inhibits multiple malignant traits, including tumor growth, metastasis, stemness and chemoresistance. Furthermore, miR‑124 influences the tumor microenvironment and modulates antitumor immune responses. These diverse functions highlight their significant potential for clinical application. Its expression is modulated by various upstream factors, including transcription factors, signaling pathways, epigenetic modifications, and other non‑coding RNAs. However, the precise mechanisms governing this upstream regulation require further investigation. Despite this, the translational application of miR‑124 for early cancer diagnosis and therapy faces several significant challenges, including improving its stability and bioavailability and developing effective in vivo delivery systems. The present study provides a comprehensive overview of the multifaceted roles of miR‑124 in cancer, elucidating its underlying molecular mechanisms and exploring its clinical potential. By synthesizing the current literature, it was aimed to consolidate the current understanding of miR‑124 and identify promising avenues for future research.

The emergence of glycosylated RNA (GlycoRNA) has expanded the paradigm of macromolecular glycosylation beyond proteins and lipids, revealing previously unrecognized layers of regulation within glycoscience and RNA biology. Increasing evidence suggests that GlycoRNA contributes to immune recognition and tumor progression. However, its biological functions and translational potential remain insufficiently characterized. GlycoRNAs are predominantly derived from small non-coding RNAs and are decorated with sialylated and fucosylated N- or O-linked glycans. Processed through canonical glycosylation pathways, they are displayed on the cell surface and contribute to tumor-immune interactions. Sialylated GlycoRNAs can bind sialic acid-binding immunoglobulin-like lectins on immune cells, generating inhibitory signaling that facilitates immune escape. Conversely, partial removal of glycans exposes modified uridine structures such as acp³U, which can activate Toll-like receptor-mediated innate immunity, indicating a glycan-dependent dual regulatory mechanism. Beyond immune regulation, alterations in GlycoRNA abundance are also associated with cancer cell migration, invasion, and metabolic adaptation. In metabolically stressful microenvironments, such as brain metastases, enhanced glycolysis increases substrates, including UDP-GlcNAc, which may further drive GlycoRNA modification and cell-surface presentation, establishing a positive feedback loop linking metabolic reprogramming to immune regulation. Given their stability on tumor cells and in circulation, GlycoRNAs represent promising biomarkers for liquid biopsy and emerging targets for immunotherapy. A comprehensive understanding of GlycoRNA glycosylation, structural determinants, and immune interactions will be essential to guide the development of diagnostic and therapeutic strategies in cancer.

Micronuclei are small, independent cytoplasmic structures containing nuclear material. They typically form during cell division due to DNA damage or division abnormalities, serve as biomarkers of genetic damage, and are closely associated with chromosomal instability (CIN). Emerging evidence suggests that micronuclei actively promote and exacerbate CIN, with significant implications in disease pathology and potential therapeutic applications. This review provides a comprehensive overview of micronuclei by exploring their origins, formation mechanisms, and functional consequences, and detailing the fate of micronuclei post-formation, which is essential for elucidating their role in genomic instability and potential therapeutic implications. Furthermore, micronuclei can contribute to extreme chromosomal shattering and genomic instability. These processes are increasingly recognized as critical contributors to disease progression, particularly in cancer. Although micronuclei have traditionally been viewed as markers of genomic instability, recent evidence suggests that they may also serve functional roles. Their potential use as treatments for certain diseases appears theoretically feasible; however, challenges remain in selectively targeting cells to induce the formation of favorable micronuclei and maintain optimal immune responses. Addressing these questions could open new avenues for therapeutic interventions.

L1 cell adhesion molecule (L1CAM) has emerged as a potential prognostic biomarker in endometrial cancer. This systematic review and meta-analysis aimed to comprehensively evaluate the prevalence of L1CAM expression across molecular subtypes of endometrial cancer and its prognostic significance for survival outcomes.

The World Health Organization introduced substantial revisions in the 2020 fifth edition of the classification system for bone and soft-tissue tumors, reorganizing what were previously called the Ewing sarcoma family of tumors or Ewing-like sarcomas into a new category of "undifferentiated small round cell sarcomas" based on molecular genetic characteristics. This reclassification established four distinct entities: Ewing sarcoma (ES), CIC-rearranged sarcoma, sarcoma with BCOR genetic alterations, and sarcoma with EWSR1-non-ETS fusion genes. Each subtype may demonstrate specific clinical, pathologic, and imaging features, with different treatment responses and prognoses. ES primarily affects children and young adults, with characteristic "moth-eaten" lytic bone destruction, aggressive periosteal reactions, and extensive surrounding soft-tissue masses. CIC-rearranged sarcomas typically manifest as well-circumscribed lobulated soft-tissue masses with extensive internal necrosis and hemorrhage but no calcification. Sarcomas with BCOR genetic alterations commonly occur in adolescent boys as osteolytic or sclerotic lesions in the long bones or the pelvis, often with calcification in the extraosseous component. Sarcomas with EWSR1-non-ETS fusion genes may manifest as osteolytic lesions with cortical expansion and saucer-like surface erosion in long bone diaphyses. Radiologic recognition of CIC-rearranged sarcomas enables oncologists to anticipate their aggressive nature and poor response to standard ES treatments, which may necessitate more intensive initial surgical interventions. In comparison, identifying BCOR-CCNB3 sarcomas through imaging allows clinicians to inform patients of their potentially more favorable outcomes compared with those of ES while still applying appropriate comprehensive treatment approaches. The authors provide an overview of the clinical features, pathologic findings, imaging characteristics, differential diagnosis, and treatment outcomes of each entity. ©RSNA, 2026.

The extracellular matrix (ECM) is a highly organised and dynamic regulator of tissue structural integrity and biochemical signalling, and its dysregulation is a hallmark of fibrosis and cancer. Recent evidence highlights the critical role of epigenetic mechanisms in controlling ECM-related gene expression and remodelling activity. This review integrates recent advances in understanding how epigenetic mechanisms govern ECM composition, remodelling, and mechanotransduction, and how reciprocal ECM-derived signals reshape the epigenetic landscape. Growing evidence links DNA methylation, histone modifications, and non-coding RNAs to the regulation of key ECM components, matrix-modifying enzymes, and stiffness-associated signalling pathways, including TGF-β, Wnt, and PI3K/Akt are summarised in this review. The bidirectional feedback between altered ECM mechanics and epigenetic enzyme activity is emphasised, showing how matrix stiffening and aberrant epigenetic programming cooperatively drive pathological tissue remodelling and tumour progression. This review summarises findings from in vitro systems, animal models, and human disease studies that illustrate the functional consequences of ECM-epigenetic crosstalk. The emerging therapeutic approaches targeting the ECM-epigenetic axis, including epigenetic modulators and ECM-directed interventions, outline current challenges and future directions for restoring matrix homeostasis in disease. Together, this review provides an integrated framework for understanding the bidirectional ECM-epigenetic interactions and their translational relevance in molecular biomedicine.

Leptomeningeal disease (LMD) is a devastating complication of advanced solid tumors with limited prognostic and response-assessment tools. Because LMD molecular evolution is frequently compartmentalized behind CNS barriers, cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) may provide CNS-specific molecular readouts of disease activity. We evaluated whether baseline CSF ctDNA profiles and longitudinal ctDNA kinetics associate with survival in LMD.

Originally reported as an oncogene and currently known to be a major "genome guardian", the p53 protein remains one of the most explored transcription factors, exhibiting variety of functions both within transcription regulation and beyond. Given that p53 dysfunction contributes to the majority of human cancers, understanding its regulatory mechanisms and therapeutic potential remains a primary research focus. This review addresses the key aspects of p53 regulation and functionality, analyses its role in tumor evolution, and provides a comprehensive analysis of current and emerging therapeutic strategies targeting the p53, with particular emphasis on immunotherapy approaches.

Mycotoxins are toxic secondary metabolites produced predominantly by fungal genera, such as Aspergillus, Fusarium, and Penicillium, and represent major foodborne contaminants responsible for chronic human exposure worldwide. While aflatoxin B1 (AFB1) is a well-established hepatocarcinogen, increasing evidence indicates that multiple mycotoxins contribute to tumorigenesis across diverse organ systems through shared biochemical and molecular mechanisms. At the molecular level, mycotoxins undergo cytochrome P450-mediated bioactivation, generating reactive intermediates that induce DNA adduct formation, oxidative stress, genomic instability, and disruption of redox homeostasis. These events converge on dysregulation of key signaling pathways governing cell-cycle control, apoptosis, immune surveillance, and epigenetic regulation, including aberrant DNA methylation, histone modification, and non-coding RNA expression. Importantly, emerging data support a "dual-hit" paradigm in which mycotoxin exposure synergizes with oncogenic viral infections, such as hepatitis B virus (HBV), human papillomavirus (HPV), and Epstein-Barr virus (EBV), amplifying genotoxic stress, immune evasion, and epigenetic instability. This review synthesizes current mechanistic insights into mycotoxin-induced carcinogenesis, emphasizing molecular toxicological endpoints that link exposure to cancer risk. In addition, advances in biosensing, detoxification, and preventive strategies are discussed, highlighting the need for mechanism-driven interventions to mitigate mycotoxin-associated carcinogenicity and its public health burden.