Pancreatic cancer is known to be one of the most challenging and complex types of cancer owing to its late diagnosis, rapid growth, and resistance to treatment. The use of iron-nickel (Fe-Ni) nanoparticles in cancer treatment is an innovative method that can reduce side effects. This study investigates the anticancer effects of Fe-Ni nanoparticles on the activity of the PANC-1 cell line.

Interleukin-1α (IL-1α) is a pleiotropic cytokine that functions both extracellularly and intracellularly; however, the mechanisms by which precursor IL-1α (pIL-1α) contributes to cytokine regulation in oral squamous cell carcinoma (OSCC) remain unclear.

Papillary craniopharyngioma (PCP) is a rare central nervous system tumor with high recurrence and significant morbidity. The BRAF V600E mutation has emerged as a potential target for treatment, with BRAF-MEK inhibitors showing promise in early studies. However, their efficacy and safety remain uncertain due to limited data from small-scale studies and case reports. This systematic review aims to evaluate the clinical outcomes of dual BRAF-MEK inhibitor therapy in BRAF V600E-mutated PCP.

Human epidermal growth factor receptor 2 (HER2/ERBB2) is a well-established therapeutic target in breast and gastric cancers, but its relevance in prostate cancer (PC) remains unresolved. Although HER2 gene amplification is relatively uncommon in PC, heterogeneous overexpression has been observed, particularly in advanced and castration-resistant PC (CRPC), where it is frequently associated with aggressive clinicopathological features. Experimental studies portray HER2 as a signaling hub, mediating crosstalk with androgen receptor (AR) signaling to sustain tumor growth under androgen-deprived conditions. Concurrent activation of the HER2-PI3K-AKT axis further promotes cell survival, proliferation, and therapeutic adaptation. Moreover, HER2 cooperates with epidermal growth factor receptor (EGFR) and NF-κB pathways, reinforcing tumor plasticity and resistance mechanisms. Despite these compelling biological insights, clinical translation has been disappointing. Early trials with Trastuzumab, Lapatinib, and Pertuzumab yielded minimal benefit, underscoring patient heterogeneity, pathway redundancy, and the lack of biomarker-guided stratification. Lessons from these failures highlight the need for precision oncology approaches that integrate molecular profiling and rational therapeutic combinations. Recent advances, including next-generation HER2-targeted antibody-drug conjugates, bispecific antibodies, and CAR-T cell therapies, as well as strategies combining HER2 inhibition with AR signaling blockade, PI3K/AKT inhibitors, or immunotherapy, offer renewed promise. HER2 in PC thus represents a paradox: biologically significant but clinically underexploited. Reframing HER2 within the AR-PI3K signaling network and leveraging biomarker-driven strategies may finally unlock its therapeutic potential. This review critically examines HER2 in PC, analyzing its mechanistic roles, therapeutic potential, and the challenges that shape its value as both a prognostic biomarker and actionable target.

miRNA-21-5p and miRNA-155-5p have emerged as two promising biomarkers in body fluids during the early stages of lung cancer. This study focused on designing a dual-target optical biosensor for the simultaneous detection of miRNA-21 and miRNA-155. DNA hairpin probes and metal nanoclusters are the materials used in this design. Light-emitting gold nanoclusters (AuNCs) and copper-silver nanoclusters (Cu/AgNCs) were located on hairpin probes to achieve fluorescence-based detection. The biosensor leverages the distinct fluorescence properties of these nanoclusters to detect target miRNAs (miRNA-21 enhances the emission of Cu/AgNCs, while miRNA-155 quenches the emission of AuNCs). The biosensor demonstrated remarkable sensitivity toward miRNA-21 and miRNA-155. Detection limits were 1 pM and 5 pM, and linear response ranges were 15-140 pM and 15-125 pM for miRNA-21 and miRNA-155, respectively. The response of the nanobiosensor was validated by RT-qPCR as the gold standard method in analyses of miRNAs in human serum samples and lung cancer cells. The obtained results confirmed the accuracy and reliability of the biosensor. Compared to existing biosensors, the proposed design avoids complex surface modifications and enzyme usage, ensuring cost-effectiveness and operational simplicity.

MicroRNAs (miRNAs) are involved in carcinogenesis. However, the biological roles and underlying mechanism of miR-3690 in head and neck squamous cell carcinoma (HNSCC) progression are far from elucidated. In this study, we found that the expression level of miR-3690 in HNSCC tissues was significantly higher and correlated with poor clinical prognosis. HNSCC cells proliferation, migration, and invasion were promoted by miR-3690 overexpression, both in vitro and in vivo. Mechanistically, miRNA pulldown DNA-seq and luciferase reporter assays revealed that miR-3690 could directly activate CKS2 expression through targeting its promoter. Meanwhile, RNA pull down and mass spectrometry (MS) analysis suggested that upregulation of CKS2 by miR-3690 correlated with increased BPTF occupancy and H3K4me3 at CKS2 promoter. Additionally, luciferase reporter assays showed that miR-3690 facilitated Wnt/β-catenin signaling in HNSCC by repressing NKD1 expression through directly targeting its 3'-UTR. Finally, methylated RNA Immunoprecipitation (meRIP) and RNA pull down indicated that METTL3 and METTL14-mediated m6A modification accelerated pri-miR-3690 maturation through regulating the processing of pri-miR-3690 by DGCR8. In conclusion, miR-3690 may be a prognostic indicator and potential therapeutic target for HNSCC.

The field of gynecologic pathology is undergoing a transformative change. The translation of molecular findings from large-scale genomic studies into clinical practice has been facilitated by robust surrogate assays, particularly immunohistochemistry (IHC). These tools provide scalable molecular proxies with short turnaround times, enabling molecular subclassification and conclusive prognostic biomarker studies. This commentary highlights how prognostic markers now refine diagnoses in challenging borderline areas, where an abnormal result can help exclude benign or precursor entities. However, the utility of these markers is highly context-dependent, modified by histotype and molecular subtype. Furthermore, the confident diagnosis of rare entities and the study of their precursors have been advanced by defining specific molecular and IHC profiles, opening new avenues for research and therapy. The integration of morphology with molecular features is increasing the robustness of diagnoses and dictating oncology management as never before.

Adult diffuse gliomas with FGFR3-TACC3 (F3T3) fusion are rare and highly heterogeneous central nervous system (CNS) tumors. Current research on the biological behavior of these tumors is limited, especially regarding whether histopathologically low-grade tumors are indolent or represent early-stage high-grade tumors, thereby posing challenges for grading. In this single-center study of 17 patients with adult F3T3 fusion diffuse gliomas (F3T3 gliomas), both low- and high-grade F3T3 gliomas presented distinctive recurrent histopathological features, such as oligodendrocyte-like cells, branched vessels and frequent calcifications. Molecularly, TERT promoter mutations and 7+/10- chromosomal alterations were common; one patient with recurrent glioma with histopathological features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) had additional CDK4 and MDM2 amplifications. Methylation profiling of 3 samples revealed varied results. A patient whose tumor had histopathological features consistent with PLNTY and a methylation subtype classified as the mesenchymal subtype of glioblastoma (GBM) experienced tumor recurrence 8 months after surgery. After 5-62 months of follow-up, seven patients relapsed, and six died; the primary tumors of the three patients with recurrence presented histopathological characteristics of low-grade glioma (LGG). GBM patients had worse overall survival than LGG patients (p = 0.035) but similar progression-free survival (p = 0.47), indicating that LGG patients may experience recurrence. For adults with tumors with histopathological features of PLNTY, further molecular and methylation analyses are needed for grading. If TERT promoter mutations are present, even with a PLNTY methylation profile, these tumors can still exhibit the biological behavior of high-grade gliomas.

Ovarian cancer remains one of the most lethal gynaecological malignancies, with paclitaxel resistance being a major therapeutic challenge that limits treatment efficacy and patient survival. We found that although the BARD1 level was not signi-ficantly altered in patients with ovarian cancer (OC), patients with higher BARD1 levels had increased survival time, suggesting that the down-regulation of BARD1 may be related to the paclitaxel sensitivity. Through examining the expression of BARD1 in tumour samples from paclitaxel responders and non-responders, we observed that the BARD1 level was significantly reduced in non-responders. CYP2C8 was up-regulated in non-responders. Also, the BARD1 level was negatively correlated with the level of CYP2C8. BARD1 over-expression in OC cells could repress the CYP2C8 expression, while knockdown of BARD1 could up-regulate CYP2C8 expression, which could be rescued by H2A-Ub. Results from gain and loss of functional experiments indicated that BARD1 functions as a tumour suppressor during paclitaxel treatment, and BARD1 down-regulation increased the IC50 of paclitaxel from 2.46 nM to 5.33 nM in SK-OV-3 cells and from 3.11 nM to 7.51 nM in CaoV-3 cells. We are the first to demonstrate that the down-regulation of BARD1 contributes to paclitaxel resistance via up-regulating CYP2C8 in patients with OC, which provides a potent target for clinical OC treatment.

Prostate cancer (PCa) represents the most common malignancy among men in many countries, including the Czech Republic. While most cases are sporadic, approximately 10 % are attributed to hereditary factors, particularly germline pathogenic variants in genes such as BRCA1 and BRCA2, ATM, and CHEK2. These variants are associated with higher disease susceptibility, aggressive tumour behaviour and earlier onset of the disease. In parallel, modifiable and non-modifiable risk factors - including age, ethnicity, lifestyle, obesity, exposure to environmental carcinogens - also play an important role in the development and progression of PCa. This review summarizes the current state of knowledge on both genetic and non-genetic risk factors for PCa and emphasizes their relevance for clinical risk stratification, early detection strategies and prevention. The paper also provides an overview of the implications of hereditary PCa in the context of targeted therapy, particularly PARP inhibitors and immunotherapy, and discusses how somatic tumour profiling may refine the therapeutic decision-making. By integrating epidemiological data, molecular diagnostic and recent clinical advances, this review enhances understanding of the genetic underpinnings of PCa and advocates for a comprehensive, precision medicine approach in PCa management. The review emphasizes the importance of early identification of high-risk individuals through germline genetic testing and polygenic risk assessment, which can guide screening and personalized treatment and ultimately improve patient outcomes.

This study aimed to identify immunologically relevant transcriptomic and proteomic biomarkers in hepatocellular carcinoma (HCC) and to characterize their B-cell epitopes for potential integration into nanomaterial-based biosensors and immunomodulatory platforms for early diagnosis and targeted therapy.

Radioresistance results in relapse and treatment failure in locally advanced colorectal cancer (CRC) patients. HMGB1 is reportedly associated with radioresistance in esophageal squamous cell carcinoma and breast cancer. However, its role in the response of CRC to radiotherapy has not been fully elucidated. Thus, we explored the role and underlying mechanism of HMGB1 in CRC radioresistance. The total amount of HMGB1 and its translocation from the nucleus to the cytoplasm increased after irradiation. Functional studies revealed that HMGB1 enhanced the proliferation and autophagy of CRC cells after irradiation. Mechanistically, HMGB1 can regulate the transcription factor ZNF460, which combines with the BECN1 promoter to promote the release of BECN1 into the cytoplasm after irradiation. Moreover, HMGB1 directly interacts with BECN1 in the cytoplasm, thereby resulting in CRC radioresistance. Finally, the protein expression levels of BECN1, which was positively correlated with HMGB1, were significantly increased in human CRC tissues and associated with TNM stage and poor prognosis in patients with CRC. Our findings revealed that HMGB1 plays a vital role in CRC radioresistance by regulating autophagy through binding with BECN1. Given the efficacy of HMGB1 modulation in CRC suppression and radioresistance, HMGB1 has emerged as a potential therapeutic molecule for CRC treatment.

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer, with EGFR mutations serving as key oncogenic drivers. However, patients harboring EGFR mutations exhibit considerable heterogeneity in clinical outcomes and treatment responses. Characterizing the malignant features of EGFR-mutant epithelial cells may facilitate improved stratification and personalized therapeutic strategies.

Energy metabolism (EM) is critically involved in driving tumor development, therapeutic resistance, and modulation of the immune response. However, its genetic basis and prognostic value in lung adenocarcinoma (LUAD) remain unclear. This study integrates multi-omics approaches to develop an EM-related prognostic model for assessing LUAD prognosis and uncovering relevant immunogenetic pathways.

N6-methyladenosine (m6A) is the most abundant internal RNA modification, orchestrated by writers, erasers, and readers. METTL14, a key component of the m6A methyltransferase complex, acts as a structural scaffold that ensures substrate recognition and modification precision. Beyond this canonical role, METTL14 regulates multiple biological processes, including chromatin remodeling, transcriptional activity, and senescence-associated signaling. Recent studies highlight its pivotal function in tumor immunity: METTL14 shapes T cell differentiation, CD8+ T cell activation, and the activity of macrophages and NK cells, thereby remodeling the tumor immune microenvironment. Moreover, METTL14 directly modulates immune checkpoint pathways by regulating PD-1 and PD-L1 expression, linking epitranscriptomic control with immune escape and therapeutic resistance. Aberrant METTL14 expression correlates with tumor progression and immune evasion, underscoring its potential as a predictive biomarker and therapeutic target. Targeting METTL14, alone or in combination with immune checkpoint inhibitors, may provide novel strategies to enhance immunotherapy efficacy.

Guidelines recommend starting average-risk colorectal cancer (CRC) screening at age 45 years, and thereafter repeating screening tests at regular intervals. However, US screening rates are currently suboptimal. This study evaluated adherence to repeat CRC screening with the non-invasive multi-target stool DNA (mt-sDNA) test among US adults.

BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) has been found to participate in cancer progression. Nevertheless, the function and mechanism of BUB1B in ovarian cancer (OC) remain unknown.

Three-dimensional (3D) culture captures key features of tumor architecture and microenvironmental signaling. Because microRNAs (miRNAs) are central post-transcriptional regulators, we asked whether 3D growth would reveal disease-relevant lncRNA-miRNA-mRNA programs in BT-474 luminal breast cancer cells.

Clinical evidence demonstrates that induction differentiation therapy is a useful treatment strategy for melanoma. Circular RNAs (circRNAs) plays a crucial role in melanoma cell proliferation, resistance and metastasis. However, the roles of circRNAs during melanoma cell differentiation have not been fully investigated. This study aimed to investigate the role and mechanism of circSipa1l1 in melanoma cell differentiation.

Circulating tumor DNA (ctDNA) is a promising biomarker for early cancer detection; however, the optimal biomarker approach for early detection of hepatocellular carcinoma (HCC) remains unclear. Furthermore, current next-generation sequencing-based detection methods remain costly and complex, limiting their clinical utility for high-risk population screening. Hence, this study compared ctDNA mutation and methylation for HCC detection and aimed to develop a clinically accessible assay. A total of 1965 participants, including 629 HCC and 1336 control participants, were enrolled in five centers. Parallel ultra-deep targeted sequencing and targeted bisulfite sequencing revealed that a methylation-based ctDNA model significantly outperformed the mutation model in detecting HCC (sensitivity, 92.1% vs. 63.7%; P < 0.001), with no added benefit from combining both markers. We subsequently developed a multiplex PCR-based bisulfite amplicon sequencing assay (MBA-seq) using 25 selected methylation markers, achieving high diagnostic accuracy (AUC = 0.958, sensitivity = 86.7%, specificity = 90.1%) in the testing set. Further refinement through AUC-based selection yielded a two-marker panel (OTX1 and HIST1H3G) adapted into a quantitative methylation-specific PCR assay, designated HCCtect. This optimized model showed robust performance (AUC = 0.925, sensitivity = 78.4%, specificity = 93.0%), significantly surpassing alpha-fetoprotein (P < 0.001) while comparable with MBA-seq. HCCtect also demonstrated efficacy in early-stage HCC detection (sensitivity = 69.5%) and discrimination from chronic hepatitis B or liver cirrhosis (specificity = 93.0%). These findings establish ctDNA methylation as a superior approach over mutation analysis and highlight HCCtect as a promising non-invasive tool for HCC detection and high-risk population monitoring.