Angiopoietin-like 7 (ANGPTL7) is a member of the angiopoietin-like protein family, which plays critical physiological roles in angiogenesis, tissue homeostasis maintenance, inflammatory signaling, glucose metabolism and lipid metabolism. Meanwhile, ANGPTL7 is also implicated in the regulation of numerous pathological processes and disease development. In recent years, several studies have demonstrated that ANGPTL7 is differentially expressed in various types of tumors and it may regulate tumourigenesis, tumor angiogenesis, invasion, and metastasis through diverse mechanisms. Additionally, ANGPTL7 has been implicated in the diagnosis and prognosis of tumor patients, suggesting its potential as a novel biomarker for tumor prediction. In this review, we provide a comprehensive overview of the structure and function of ANGPTL7, as well as its role and underlying mechanisms in tumor development. Furthermore, we discuss potential future research directions and clinical applications of ANGPTL7 in oncology.

Acute myeloid leukemia (AML) is a biologically heterogeneous and clinically aggressive hematologic malignancy defined by the clonal expansion of immature myeloid progenitors, resulting in progressive bone marrow (BM) failure, peripheral cytopenias, and fatal infectious or hemorrhagic sequelae. The adverse clinical outcomes associated with AML arise from the combined effects of disrupted physiological hematopoiesis, persistence of therapy-refractory leukemic stem cells (LSCs), and extensive inter- and intratumoral genetic and epigenetic heterogeneity that underlies rapid disease progression and relapse. AML constitutes a prototypical disorder of hematopoietic dysregulation, wherein aberrant self-renewal capacity and arrested differentiation programs drive malignant transformation through the integrated influence of recurrent genomic lesions, epigenetic reprogramming, metabolic alterations, dysregulated signaling cascades, and reciprocal interactions with the BM microenvironment. These processes collectively reconfigure transcriptional landscapes and cellular hierarchies within the leukemic compartment. The objectives of this review are to provide an integrated framework for understanding AML pathobiology encompassing chromosomal abnormalities, transcriptional and epigenetic regulatory networks, and microenvironmental cues and to emphasize emerging analytical paradigms, including integrative multi-omics, single-cell and spatial technologies, and system-level approaches, which are reshaping conceptual models of malignant hematopoiesis and accelerating the development of mechanism-based therapeutic strategies.

Primary central nervous system (CNS) neuroblastoma, FOXR2-activated (CNS-NB-FOXR2), is a rare embryonal tumor characterized by neuroblastic differentiation and structural rearrangement of the FOXR2 gene. Previously grouped under CNS primitive neuroectodermal tumors (PNET), this entity has been reclassified based on genome-wide DNA methylation profiling. In this study, we present the detailed clinicopathological and immunohistochemical features of two pediatric cases diagnosed at our center. The first case involved a six-year-old with a left frontal mass; the second was a one-year-old with a large bifrontal lesion. Radiologically, both cases mimicked other embryonal tumors or high-grade gliomas. Histologically, tumors displayed small round blue cell morphology with neuroblastic features, including Homer-Wright rosettes and ganglionic differentiation. Immunohistochemistry demonstrated diffuse positivity for OLIG2, synaptophysin, and L1CAM, with negative expression for GFAP, EMA, and IDH1 R132H. FOXR2 showed nuclear positivity in both cases, supporting the diagnosis. Both cases exhibited diffuse L1CAM positivity-a rare finding with limited evidence in the existing literature. Although DNA methylation profiling could not be performed, the diagnosis was supported by characteristic morphology and immunohistochemistry profile. This report highlights key diagnostic features and potential mimics of CNS neuroblastoma, FOXR2-activated, and underscores the utility of immunohistochemistry in low-resource settings. Recognizing this entity is essential for accurate classification and appropriate therapeutic planning. Further studies are warranted to explore targeted therapies, including MEK inhibitors, which may hold promise based on emerging molecular data.

There has been a paradigm shift in the pathogenesis mechanisms of cancer over the past few decades in oncology, whereby the regulators of tumorigenesis are non-coding RNAs (ncRNAs). Circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) have also recently been of great interest due to their roles as regulatory molecules in pathological processes, including cancer. These regulatory molecules operate partially by interfering with kinesin superfamily proteins (KIFs)-cellular molecular motors implicated in the transport phenomena within a cell and related processes, including post-mitotic and basic cell functions. Cumulative evidence shows that ncRNA-KIF networks operate through independent mechanistic pathways. In most cases, circRNAs function as competitive endogenous RNAs by sequestering microRNAs and modulating the indirect pathway of KIF expression. lnRNAs can bind protein or mRNA of KIF directly and modify its function or stability. Briefly, they all share a broad range of cancer hallmarks such as heightened proliferative signaling pathways, drug resistance, and invasion and metastasis. Several ncRNA-KIF axes are tissue-specific in the three cancers, namely glioblastoma, breast cancer, and colorectal carcinoma, and thus are also potential therapeutic targets, along with biomarkers. The clinical relevance of this finding is that strong ncRNA-KIF signatures would likely allow for the early detection of cancer with a favorable prognosis; such interactions would unveil novel therapies, particularly in therapy-refractory tumors. For example, inhibiting oncogenic ncRNA-KIF networks or restoring tumor-suppressive ones would be related to all existing methods. With advancing science, a progressively more evolved view of such regulatory networks will reveal increasingly complex layers in cancer biology and identify novel targets for RNA-based therapies. Such advances in new knowledge underscore the importance of extending current research into ncRNA-KIF interactions and their translational relevance to precision oncology.

In metastatic melanoma with a BRAFV600 mutation, inhibitors of BRAF and MEK have improved survival. Resistance may be acquired through late genetic alterations that restore mitogen-activated protein kinase (MAPK) signaling. Resistance can also be adaptive, involving early and reversible transcriptional or metabolic shifts that generate drug-tolerant cells, or intrinsic, arising from pre-existing conditions such as phosphatase and tensin homolog (PTEN) loss or an AXL receptor tyrosine kinase-high (AXL-high) state. For instance, some tumors exhibit phenotypic plasticity, dynamically switching between AXL-high invasive and microphthalmia-associated transcription factor-high (MITF-high) proliferative cell states, leading to relapse after an initial response. When compared to upfront targeted therapy, first-line immune checkpoint blockades typically confer greater long-term survival, according to major clinical trials examining therapeutic sequencing (DREAMseq, SECOMBIT, EBIN). BRAF and MEK inhibitors remain effective when used as second-line therapy, and high-risk patients can safely achieve quick tumor control without sacrificing results by receiving a brief course of targeted therapy prior to immunotherapy. To enable precision-guided adaptive dosage, (ctDNA) has emerged as a valuable biomarker for early detection of resistance mutations and real-time monitoring of disease dynamics. The article concludes that new investigational approaches to overcoming resistance include triplet regimens (targeted therapy plus immunotherapy), co-targeting alternative pathways (such as AXL receptor tyrosine kinase-high (AXL) or phosphoinositide 3-kinase-AKT (PI3K-AKT)), and incorporating radiotherapy to eradicate resistant clones. However, strategies such as intermittent (adaptive) dosing have failed to improve outcomes in clinical trials. Ongoing trials and advances in artificial intelligence-driven personalization may further refine treatment selection and improve long-term outcomes.

Glioblastoma is a highly aggressive primary brain tumour marked by extensive genomic and epigenomic alterations, cellular heterogeneity, and therapeutic resistance. Despite maximal surgical resection followed by chemoradiotherapy, median survival remains approximately 15 months, reflecting the tumour's invasive behaviour and adaptability. Advances in molecular oncology have revealed two promising therapeutic directions: epigenetic reprogramming and neurogenetic modulation. Glioblastoma exhibits widespread epigenetic dysregulation that disrupts transcriptional control, enhances cellular plasticity, and drives tumour progression. Concurrently, glioma cells aberrantly reactivate developmental programmes, acquiring neural stem cell-like states governed by transcription factors and signalling networks such as SOX2, OLIG2, Notch, and Wnt. These pathways collectively sustain stemness, lineage mimicry, and therapy resistance. This review proposes a focused conceptual framework centred on epigenetic and neurogenetic modulation as two core regulatory layers shaping glioblastoma plasticity and adaptive resistance. We highlight how DNA methylation, histone modifications, and chromatin remodelling contribute to transcriptional dysregulation, and how neurodevelopmental signalling reinforces malignant plasticity. Emerging preclinical and clinical studies combining epigenetic inhibitors with differentiation- or reprogramming-based therapies are discussed. By uniting mechanistic insights from chromatin biology, neurodevelopment, and cancer therapeutics, this integrative conceptual framework offers a structured lens for targeting key vulnerabilities underlying glioblastoma plasticity. The integration of these complementary strategies offers potential to enhance therapeutic responsiveness and improve disease management in this devastating malignancy.

PSMD9/Nas2/Bridge-1 is one of the assembly chaperones of the 19S regulatory particle of the eukaryotic proteasome. While this is among PSMD9's well-recognized roles, the role of PSMD9 in cancer proteasome assembly/disassembly and activity, as a key factor in the ubiquitination and degradation of proteins by the proteasome, unfolded protein response, and proteostasis, nucleolar organization, are some of the recent findings. Several unbiased screening, high-throughput studies, genome-wide association studies (GWAS) have found surprising associations and potential roles for PSMD9 in a variety of diseases or conditions. Although in a majority of these cases the mechanism remains unclear, it is important to take note that this multi-functional protein, in the absence of any enzymatic role, relies primarily on its ability to interact with other proteins and biomolecules in the cells. A surprising range of proteins that associate with PSMD9 discovered by the structure-guided approaches overlaps with many different functions associated with this protein or the proteasome in literature. Collective evidence also points to the possibility that PSMD9 could be an Achilles' heel in some of the solid cancers.

Immigration of Asians and Hispanics to countries with higher affluence is associated with a marked increase in the incidence of prostate and other cancers. The goal of this review was to understand the genomic mechanism.

Mismatch repair deficiency (dMMR) and microsatellite instability (MSI-H) cancers exhibit high immunogenicity and are highly responsive to immune checkpoint inhibitors. In patients with locally advanced dMMR/MSI-H colorectal cancer (CRC), neoadjuvant immunotherapy (NIT) has demonstrated unprecedented pathological complete response (pCR) rates, suggesting nonoperative management strategies may be possible. There remains a discrepancy between radiological assessment and pathological responses to NIT in CRC.

Tumor-derived circulating cell-free DNA (ctDNA) has emerged as a pivotal biomarker for non-invasive cancer diagnosis, treatment monitoring, and prognostic evaluation. However, its inherently low abundance, high fragmentation, and rapid degradation impose stringent requirements on assay sensitivity, specificity, and analytical robustness. Rapid advances in nanotechnology have significantly accelerated progress in ctDNA detection. This review summarizes recent nanotechnology-assisted strategies for ctDNA analysis, including surface-engineered nanomaterials for selective enrichment, nano-enabled signal amplification modalities, and integrated platforms such as CRISPR-based detection, microfluidics and nanopore technologies. We further highlight nanostructure-based approaches for decoding methylation, fragmentation profiles, and multi-omics signatures, focusing on their potential to enhance early cancer detection and real-time therapeutic assessment. Moreover, increasing incorporation of artificial intelligence (AI) which spans nanostructure characterization, aptamer and probe design, multi-omics data integration, and algorithm development is reshaping the landscape of nano-assisted liquid biopsy. Finally, current challenges and future perspectives concerning the clinical translation of nanotechnology-assisted ctDNA detection are presented, emphasizing standardization, biocompatibility, automation, and regulatory readiness. Overall, this review provides a comprehensive outlook on how converging nanotechnology and AI innovations are advancing ctDNA-based precision oncology.

Epidermal growth factor receptor ( EGFR ) is a critical driver gene in non-small cell lung cancer (NSCLC). Since 1997, EGFR tyrosine kinase inhibitors (EGFR-TKIs) have evolved from first-generation agents, such as gefitinib, erlotinib, and icotinib, to second-generation agents like afatinib and dacomitinib, now to third-generation agents, including osimertinib, aumolertinib, furmonertinib, befotertinib, rezivertinib, rilertinib, limertinib, lazertinib, mifanertinib for EGFR L858R, sunvozertinib for EGFR exon 20 insertion (20ins), and zorifertinib for EGFR -sensitive mutation with brain metastases. Throughout this evolution, EGFR-TKIs have become the cornerstone of treatment for EGFR -mutant NSCLC, extending beyond advanced stages to encompass the entire disease spectrum, including perioperative and maintenance therapies, with combination therapies further expanding treatment options. These advancements have significantly improved patient survival and quality of life. However, challenges such as acquired resistance remain significant hurdles in achieving long-term disease control. Over the past 30 years, substantial advancements have been made in the comprehensive management of EGFR -mutant NSCLC. This systemic review provides the history of the development of EGFR-TKI therapy for NSCLC from 1997 to 2026, highlighting clinical milestones, emerging therapies, and future directions in this rapidly evolving field.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is characterized by extensive immune infiltration, yet immune evasion remains a hallmark. In this study, we aimed to leverage publicly available datasets to identify EBV-host gene interactions and re-map their expression at single-cell resolution. We conducted a meta-analysis to identify differentially expressed genes, mapped these genes to EBV-host interaction data, constructed a network, and performed pathway enrichment. Single-cell RNA sequencing datasets were used to map these genes at cellular resolution. We analysed differences in cell cycle, immune signaling, cell-cell interactions, and assessed prognostic associations of UPS signature using the GEPIA2 platform. We identified 85 EBV-interacting DEGs regulated by lytic-phase proteins. Clustering highlighted genes related to the ubiquitin-proteasome system (UPS). Single-cell analyses confirmed elevated UPS-related gene expression in NPC. UPS-High cells exhibited lower proliferative activity, enriched stemness signaling, and reduced antigen presentation and immune activation, whereas UPS-Low cells showed marked upregulation of growth-promoting pathways. High UPS expression was associated with poorer outcomes in pan-cancer, head and neck squamous cell carcinoma, and marginally significant in the small NPC datasets. The proportion of UPS-High cells varied widely across patients. UPS activity, influenced by EBV lytic proteins, is linked to immune evasion, stemness, proliferation, and adverse prognosis. These findings support UPS as a potential biomarker and therapeutic target in NPC, warranting validation and functional studies.

FLT3 mutations drive acute myeloid leukemia (AML) progression through aberrant signaling, making FLT3 inhibition a key therapeutic strategy. Current inhibitors show efficacy, yet resistance and toxicity remain challenges. Emerging approaches, including selective inhibitors, proteolysis-targeting chimeras, and protein degraders, offer enhanced potency, sustained suppression, and combinatorial potential, representing a precision-based advancement in AML treatment.

Melanoma remains the most lethal form of skin cancer despite major advances in targeted and immune-based therapies. Biomarkers now play central roles in diagnosis, risk stratification, therapeutic selection, and disease monitoring; however, their clinical integration remains inconsistent. This review synthesizes the evolving biomarker landscape across genetic (e.g., BRAF, NRAS, KIT, TERT, NF1, CDKN2A), immune (PD-L1, LAG-3, TIGIT, TILs, TMB), proteomic (S100B, MMPs, signaling signatures), and digital/imaging biomarkers (AI-assisted dermo copy, spatial and multiplex profiling). We highlight subtype-specific differences in mucosal, acral, and uveal melanoma, where biomarker patterns and therapeutic responses diverge markedly from those of cutaneous disease. Liquid biopsy approaches, including ctDNA, methylation signatures, and extracellular vesicles, are evaluated for minimal residual disease detection and resistance monitoring. To advance clinical translation, we propose a standardized, stepwise diagnostic therapeutic framework integrating tissue- and blood-based biomarkers with AI-enabled imaging to support personalized management in both adjuvant and metastatic settings. Key translational enablers include assay harmonization (PD-L1, TMB, ctDNA), evidence-tiered validation, and pragmatic clinical trials incorporating biomarker-driven endpoints. Addressing cost, accessibility, and data ethics will be essential for biomarker-guided precision oncology to become a sustainable clinical reality across diverse health systems.

With over 968,000 new cases and approximately 660,000 deaths reported in 2022, gastric cancer represents a global health burden. Despite rising evidence from animal and organoid models identifying spasmolytic polypeptide-expressing metaplasia as a critical precancerous lesion, the mechanisms governing its initiation and progression remain incompletely understood. This review situates spasmolytic polypeptide-expressing metaplasia within the classical Correa cascade and synthesizes current literature by categorizing the underlying mechanisms into six distinct domains: paligenosis, intracellular redox homeostasis, oncogenic pathways, inflammatory responses, parietal cell lineage, and cancer-associated fibroblasts. Furthermore, this article comprehensively summarizes in vivo/vitro and human models of spasmolytic polypeptide-expressing metaplasia, aiming to provide a practical framework for future investigations and, ultimately, to offer novel perspectives on the prevention, diagnosis, and treatment of gastric cancer.

Genetic mutations and their phenotypic manifestation have been recognized as critical factors in tumorigenesis. However, the relationship between these mutations and the pathogenesis of uterine leiomyomas (UL) remains inadequately characterized. There is compelling evidence to suggest a genetic underpinning in UL development, alongside influences from epigenetics, environmental stimuli, growth hormones, and growth factors. A plethora of studies have tried to elucidate the genetic and epigenetic etiologies associated with UL, but the definitive implications of these findings remain unclear. An extensive systematic review was conducted to investigate the genetic etiologies of UL. This systematic review aimed to consolidate current knowledge on genetic and epigenetic causes of UL, offering a comprehensive perspective on the evidence and its relevance in other solid tumors. A secondary focus was to identify the most significant genetic association with the genesis of UL. A total of 60 articles were identified, and 10 chromosomes and 51 genes were found to be implicated in the development of UL. The main trend in fibroid research focuses on genetic abnormalities and aberrations as the etiology of UL development. It has been estimated that 40% of UL can be associated with chromosome-specific aberrations. Chromosomal gain, loss, rearrangement, single nucleotide polymorphism (SNP), and translocation are the most common aberrations associated with UL development. The most recurrent ones include chromosome X and 7q deletions, and rearrangements of 12q15, 6p21 and 10q22. MED12 has been identified as a gene of particular importance in the development of UL.

Sunvozertinib (DZD9008) is an emerging next-generation, highly selective EGFR tyrosine kinase inhibitor (TKI) designed to target EGFR exon 20 insertion (Ex20ins) mutations, a subtype of non-small cell lung cancer (NSCLC) associated with poor response to earlier-generation EGFR TKIs. Patients with these mutations typically exhibit intrinsic resistance to approved standard EGFR inhibitors due to the altered conformation of the kinase domain. Consequently, therapeutic options have remained limited, and platinum-doublet chemotherapy has historically been the primary systemic treatment. Recently developed agents such as amivantamab and mobocertinib have improved response rates, yet challenges related to tolerability, CNS penetration, and durability of benefit persist. Sunvozertinib aims to address these limitations through rational structural design, optimized kinase selectivity, and improved safety-efficacy balance. Preclinical studies have shown potent inhibition of a broad spectrum of EGFR Ex20ins variants while sparing wild-type EGFR, suggesting a reduced risk of dose-limiting toxicities commonly seen with non-selective EGFR blockade. Sunvozertinib has also demonstrated promising CNS activity in animal models-an important feature for NSCLC patients, who frequently develop brain metastases. Early-phase clinical trials, including the WU-KONG series, have reported promising clinical efficacy, including objective response rates ranging from 44-60% in previously treated patients and meaningful activity in treatment-naïve cohorts. The tolerability profile of the drug seems manageable, with diarrhea, rash, and stomatitis among the most commonly observed adverse events; these, however, tend to be milder compared with other agents targeting EGFR Ex20ins.

The long non-coding RNA HOTAIR has been implicated in tumor initiation and progression, and multiple case-control studies have explored whether common HOTAIR single-nucleotide polymorphisms influence susceptibility to gastrointestinal (digestive system) malignancies. However, published findings remain inconsistent across populations and cancer types.

Lung cancer exhibits one of the highest incidence and fatality rates globally. With the advancement of next-generation sequencing testing techniques, double or multiple gene driver mutations have been identified in certain patients.

Antibody-related immune phenotypes reflect long-term host-pathogen interactions and immunogenetic regulation, and have been increasingly implicated in cancer susceptibility. In ovarian cancer, observational associations between immune responses and disease risk remain difficult to interpret due to confounding and potential reverse causation. Genetic analyses may help clarify whether specific antibody immune response profiles are linked to ovarian cancer risk. We investigated the associations between 46 genetically predicted antibody immune response phenotypes and ovarian cancer using a 2-sample Mendelian randomization framework. Genetic instruments for antibody traits were obtained from large genome-wide association studies, while ovarian cancer summary statistics were derived independently from the FinnGen R12 and OpenGWAS resources. Causal estimates were derived primarily using inverse-variance weighted models and subsequently synthesized across datasets to improve precision. Multiple testing adjustment was applied, and additional analyses were conducted to assess robustness and causal directionality. Across the evaluated antibody phenotypes, most showed no evidence of a causal association with ovarian cancer risk. After meta-analysis and correction for multiple comparisons, genetically predicted anti-polyomavirus 2 immunoglobulin G (IgG) seropositivity was associated with a modest increase in ovarian cancer risk (odds ratio = 1.062, 95% confidence interval: 1.027-1.099). Sensitivity analyses did not indicate substantial pleiotropic bias, and reverse-direction analyses provided no support for ovarian cancer influencing anti-polyomavirus 2 IgG levels. These findings suggest that genetic liability to anti-polyomavirus 2 IgG seropositivity, as a marker of immune response rather than active infection, is modestly associated with ovarian cancer risk in individuals of European ancestry. Although the effect size is small, the results highlight a potential role for antibody-mediated immune processes in ovarian cancer etiology and warrant further investigation in diverse populations and experimental settings.