Cisplatin resistance remains a major obstacle in advanced gastric cancer (GC). This study aimed to identify key molecular determinants of cisplatin resistance, with a focus on interferon-stimulated genes (ISGs), and to systematically investigate the functional role of interferon-stimulated gene 15 (ISG15) in mediating chemoresistance.

Cervical cancer remains a significant global challenge, necessitating novel therapeutic strategies beyond conventional radiotherapy and chemotherapy. The anticancer potential of natural compounds has recently garnered increased recognition. This study aimed to expand this knowledge by exploring the molecular mechanisms by which spinach extract (SE) influences the growth and survival of HeLa cervical cancer cells.

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.

Oligodendrogliomas are rare malignant brain tumors with median survivals exceeding fifteen years after treatment with chemoradiation therapy. Long lifespans increase risk for adverse treatment effects. We retrospectively reviewed outcomes after early upfront radiation therapy (RT) or RT deferred until disease progression to determine whether toxicity and survivals were different.

Prostate cancer is one of the most common malignancies in men. Although androgen deprivation therapy (ADT) offers substantial benefit, resistance to androgen signaling ultimately develops, leading to castration-resistant prostate cancer (CRPC). Approximately 10-17% of CRPC cases evolve into treatment-induced neuroendocrine prostate cancer (t-NEPC), an aggressive, androgen receptor (AR)-independent subtype. The TMPRSS2-ERG fusion gene is among the most frequent genomic alterations in prostate cancer; however, its involvement in t-NEPC development remains unclear.

Bladder cancer (BLCA) is a prevalent malignancy globally, particularly in Taiwan, where its incidence continues to rise. While environmental exposures such as smoking play critical roles in BLCA etiology, genetic predispositions also contribute significantly. Matrix metalloproteinase-2 (MMP-2), a key enzyme involved in extracellular matrix remodeling, has been implicated in BLCA progression. This study investigated the associations of two promoter polymorphisms in the MMP-2 gene, rs243865 and rs2285053, with BLCA susceptibility in a Taiwanese population.

Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to gemcitabine (GEM) resistance. This study aimed to establish a clinically relevant immunocompetent model to identify novel mediators of acquired GEM resistance.

We found epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) is up-regulated in liver cancer cells exposed to sorafenib for a long time using a bioinformatic tool. Here, the mechanism of EFEMP1 in sorafenib resistance of hepatocellular carcinoma (HCC) cells was explored.

Hereditary cancer risk is key to guiding screening and prevention strategies. Cancer risks can vary by individual because of the presence or absence of high- and moderate-risk pathogenic variants (PVs) in cancer-associated genes, in addition to sex, age, and other risk factors. We previously developed Fam3PRO, a flexible multigene, multicancer Mendelian risk prediction model that estimates a patient's risk of carrying a PV in hereditary cancer genes and their future risk of developing several types of cancers. The Fam3PRO R package includes 22 genes with 18 associated cancers, allowing users to build customized submodels from any gene-cancer set. However, the current R package lacks a user interface (UI), limiting its practical use in clinical settings. Therefore, we aim to develop a web-based UI for broader use of the Fam3PRO functionalities.

Acute myeloid leukemia (AML) is a hematopoietic malignancy caused by abnormal proliferation and differentiation of blasts. PRMT5, a methyltransferase that catalyzes symmetric dimethylation of arginine (SDMA) residues, has been implicated in cancer stem cell homeostasis and shown to be a potential therapeutic target in AML. However, given the toxicity of complete PRMT5 inhibition, there is a need to identify effective synergistic therapies. Through a targeted screen of compounds that inhibit key nodes of PRMT5-regulated pathways, we identified a synthetic lethality between inhibition of PRMT5 and LSD1, a lysine demethylase known to affect AML blast differentiation. The two inhibitors broadly reshape the transcriptome of targeted cells and synergize to promote AML differentiation and eventually growth inhibition and apoptosis, in a p53-dependent manner. To leverage this synthetic lethal interaction, we generated new dual compounds to inhibit both enzymes and recapitulated the effects of the drug combination. Our results uncover an unexpected convergence of PRMT5- and LSD1-regulated targets, paving the way for new therapeutic opportunities.

Genome aneuploidy, characterized by copy number variations (CNVs), profoundly alters gene expression in cancer through direct gene dosage effects and indirect compensatory regulatory mechanisms. However, existing differential gene expression (DGE) testing methods do not differentiate between these mechanisms, conflating all expression changes, limiting biological interpretability and obscuring key genes involved in tumor progression. To address this, we developed DeConveil, a computational framework that extends traditional DGE analysis by integrating CNV data. Using a generalized linear model with a negative binomial distribution, DeConveil models RNA-seq expression counts while accounting for copy number gene dosage effects. We proposed a more fine-grained gene decomposition into dosage-sensitive (DSGs), dosage-insensitive (DIGs), and dosage-compensated (DCGs), which explicitly de-couples changes due to CNVs and bona fide changes in transcriptional regulation. Analysis of TCGA datasets from aneuploid solid cancers resulted in notable reclassification of genes, refining and expanding upon the results from conventional methods. Functional enrichment analysis identified distinct biological roles for DSGs, DIGs, and DCGs in tumor progression, immune regulation, and cell adhesion. In a breast cancer case study, DeConveil's CN-aware analysis facilitated the identification of both known and novel prognostic biomarkers, including lncRNAs, linking gene expression signatures to survival outcomes. Utilizing these biomarkers for each gene group significantly improved patient risk stratification, yielding more accurate predictions compared to conventional methods. These results highlight DeConveil's ability to disentangle CNV-driven from regulatory transcriptional changes, enhancing gene classification and biomarker discovery. By improving transcriptomic analysis, DeConveil provides a powerful tool for cancer research, precision oncology, with potential applications in therapeutic target identification.

Breast cancer (BC) is the most commonly diagnosed cancer among women globally, with significant regional variations in its molecular subtypes, clinical presentation, and management. Despite advancements in oncology, limited data exist on the molecular and clinical characteristics of BC in Libya. This study aims to analyze the prevalence of molecular subtypes, clinicopathological features, and treatment patterns among Libyan women with BC at Tobruk Medical Center. This retrospective observational study included BC patients diagnosed between January 2019 and December 2020 at Tobruk Medical Center. Demographic, clinical, pathological, and treatment-related data were extracted from medical records. Molecular subtyping was based on immunohistochemical assessment of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67. Statistical analyses were performed using SPSS version 28 (IBM Corp., Armonk). Among 115 patients analyzed, the median age at diagnosis was 46 years. Invasive ductal carcinoma accounted for 89.6% of cases, with grade II tumors being the most common (69.6%). Luminal B was the predominant molecular subtype (67.8%), followed by luminal A (14.8%), HER2-enriched (10.4%), and triple-negative BC (7.0%). Advanced-stage diagnoses (stage III and IV) were observed in 57.4% of cases. Hormone receptor positivity was detected in 82.6%, and HER2 positivity in 25.2% of cases. This study highlights the high prevalence of advanced-stage BC and the predominance of the aggressive luminal B subtype in Libya. Targeted early detection programs and improved treatment access are urgently needed to address these challenges.

This study aims to investigate the effects of long noncoding RNA myocardial infarction-associated transcript (lncRNA MIAT) targeting miR-361-3p on the proliferation, invasion, and apoptosis of hepatocellular carcinoma (HCC) cells. The expression levels of lncRNA MIAT and miR-361-3p were examined in both cancerous and adjacent non-tumorous tissues of HCC patients. Additionally, their expression was analyzed in THLE-2 and MHCC97L cells. MHCC97L cells were transfected to observe changes in relevant mRNA expression and alterations in cell proliferation, invasion, and apoptosis. Compared with adjacent non-tumorous tissues, cancerous tissues exhibited increased levels of lncRNA MIAT mRNA and decreased levels of miR-361-3p (P < .05). Elevated transcription levels of lncRNA MIAT were more prevalent in patients with lymph node metastasis and advanced TNM staging (P < .05). In MHCC97L cells, compared with THLE-2 cells, there was an increase in lncRNA MIAT mRNA and a decrease in miR-361-3p (P < .05). LncRNA MIAT and miR-361-3p were found to have potential binding sites and exhibit target regulation. Cells in the miR-NC group showed no significant changes in all indicators compared with the negative control group (P > .05). Conversely, cells with low expression of lncRNA MIAT and cyclin D1 mRNA and decreased cell proliferation and invasion numbers showed increased expression of miR-361-3p and phosphatase and tensin homolog mRNA and higher apoptosis rates (P < .05). The group with elevated expression levels demonstrated contrasting patterns (P < .05). LncRNA MIAT is upregulated in HCC tissues. Silencing lncRNA MIAT can elevate miR-361-3p levels, inhibiting the proliferation and invasion of MHCC97L cell structures and promoting apoptosis.

Tertiary lymphoid structures (TLSs) are critical components of the tumor microenvironment in HCC. However, the role of TLS-related molecules in predicting HCC outcomes and guiding immunotherapy remains unexplored. This study aimed to develop TLS-related gene signature (TLSRS) to predict prognosis and immunotherapy response in patients with HCC​​​​​​.

Esophageal squamous cell carcinoma (ESCC) is among the most lethal malignancies worldwide, with a five-year survival rate below 20%. Ferroptosis-a regulated form of cell death driven by iron-dependent lipid peroxidation-has emerged as a promising therapeutic strategy, yet its regulation in ESCC remains poorly understood. We investigated the role of tripartite motif-containing 31 (TRIM31), an E3 ubiquitin ligase, in ESCC progression and ferroptosis.

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.

POLE2 exhibits oncogenic properties. This study aimed to clarify its effects and underlying mechanisms in renal cell carcinoma (RCC). Using bioinformatics analyses, we predicted the relationship between POLE2 and autophagy, epithelial-mesenchymal transformation (EMT), and the AKT/mTOR pathway. The expression pattern of POLE2 was further verified in the clinical cohort comprising 94 tumor samples from patients with RCC. Following, we constructed in vivo and in vitro models to further investigate the potential mechanisms of POLE2 using a series of molecular biology approaches. The results showed that GINS1 was the downstream target of POLE2, and its overexpression reversed the inhibitory effects of POLE2 knockdown on RCC proliferation, metastasis, and EMT, while restoring the autophagy suppression. Furthermore, POLE2/GINS1 inhibited AKT/mTOR-mediated autophagy, thereby promoting EMT and lung metastasis of RCC. These findings provide a more comprehensive perspective on the genetic function of POLE2 in RCC progression.

Background/Objectives: To evaluate the immunohistochemical expression of hexokinase-2 (HK2), glutaminase-1 (GLS1), and fatty acid synthase (FASN) and its prognostic significance in diffuse gastric adenocarcinoma. Materials and Methods: Formalin-fixed paraffin-embedded tissue samples from 92 patients with diffuse gastric adenocarcinoma were analyzed. Immunohistochemistry (IHC) was performed to assess the expression of HK2, GLS1 and FASN. Expression levels were evaluated semi-quantitatively based on staining intensity and the percentage of positive cells. Associations between enzyme expression and clinicopathological features were assessed using the Chi-square test. Kaplan-Meier survival analysis was employed to evaluate progression-free survival (PFS) and overall survival (OS) and the log-rank test and Cox proportional hazards models were used for statistical analysis. Results: HK2 and FASN were overexpressed in 20.7% and 22.8% of patients, respectively, and were significantly associated with advanced tumor stage. In contrast, GLS1 expression, found in 30.4% of patients, did not independently correlate with clinicopathological characteristics. Furthermore, HK2 expression and co-expression of HK2/FASN (10.9%) and HK2/GLS1/FASN (8.7%) were associated with progressive disease. In the univariate analysis, stage, HK2 overexpression, and co-expression of HK2/FASN and HK2/GLS1/FASN were associated with shorter survival. However, only stage retained prognostic value in the multivariate analysis. Conclusions: Co-expression of these key metabolic enzymes remains a promising candidate as prognostic markers and therapeutic targets. Concurrent targeting of these metabolic pathways may offer novel therapeutic opportunities for patients with advanced-stage gastric cancer.

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.

Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy in which numerous biomarker candidates have been reported, yet few progress to clinical use. Beyond biological complexity, this low translational yield reflects the lack of systematic criteria for prioritizing biomarkers during the discovery stage. In particular, tumor-derived signals identified in tissue often fail to persist in clinically accessible biofluids, as cross-compartment signal behavior is rarely evaluated explicitly.