Search Results (38,620)

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

Oxicam derivatives, a class of nonsteroidal anti-inflammatory drugs (NSAIDs), are important scaffolds for developing biologically active compounds. In this study, arylpiperazine oxicam derivatives (PR24–PR50) were examined for membrane interactions, cytotoxic activity, cyclooxygenase inhibition, and potential binding to COX-2 protein. Membrane interactions were examined using differential scanning calorimetry (DSC) in phospholipid bilayers formed from 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). All compounds altered the thermotropic properties of the lipid bilayer, showing concentration-dependent decreases in phase transition temperature, indicating incorporation to bilayer and partial disruption of lipid organization. Cytotoxicity, assessed using the MTT assay in breast cancer (MCF-7, MCF-7/DX), colorectal cancer (LOVO, LOVO/DX), and normal V79 cell lines, showed moderate effects, particularly against colorectal cancer cells. Cyclooxygenase inhibition was rather weak, with IC₅₀ values in the high micromolar range, indicating limited anti-inflammatory potential compared with reference COX inhibitors, although docking studies suggested possible interactions with the COX-2 active site. The obtained results indicate that the biological activity of the arylpiperazine oxicam derivatives is primarily associated with cytotoxicity and membrane effects rather than COX inhibition. These limitations should be considered in the design of future membrane-targeted bioactive compounds. Full article

American Indian and Alaska Native (AI/AN) populations experience disproportionately high kidney cancer incidence and mortality compared to other groups in the United States. Literature was reviewed to explore the factors contributing to the unequally higher kidney cancer burden in AI/AN communities and to develop recommendations to reduce these disparities. The incidence of kidney cancer has been rising over the past few decades, and this increase has been especially steep among AI/AN populations. Death rates in AI/AN populations are roughly twice those of the non-Hispanic White population. The elevated kidney cancer burden in AI/AN populations may be driven by both clinical and behavioral risk factors (obesity, diabetes, hypertension, chronic kidney disease, smoking, and environmental factors) and structural drivers of health, which can critically shape these disparities. Systemic inequalities limit AI/AN patients and community members’ access to chronic disease management, smoking cessation programs, primary and specialty care for early detection, and ultimately, treatment. AI/AN patients may have mistrust or other cultural barriers to engaging with the healthcare system and providers, while implicit bias in healthcare providers may lead to undertreatment. Therefore, key interventions and tailored programs aimed at reducing kidney cancer incidence and mortality are needed. Here we highlight some current interventions, including access to disease management and smoking cessation programs, facilitating healthcare access and quality, adopting patient navigation and culturally competent education, and developing strategies for early detection. In partnership with AI/AN communities, a combination of prevention, early detection, and healthcare system improvements is needed to close the kidney cancer gap. Full article

Dpep is a cell-penetrating peptide that targets transcription factors ATF5, CEBPB and CEBPD to selectively suppress growth and survival of diverse tumor cell types in vitro and in vivo. Due to these actions and its apparent safety, the peptide has potential as a cancer therapeutic. How Dpep might be combined with other anti-cancer agents to achieve synergistic efficacy and to overcome possible peptide resistance has not been assessed in depth. Based on prior work indicating that Dpep promotes apoptotic cancer cell death and up-regulates multiple pro-apoptotic and tumor suppressor genes, we studied combinations of Dpep with ABT-263, a pro-apoptotic BCL2 family inhibitor, and decitabine, a hypomethylating drug. Combining Dpep with each agent alone or together synergistically suppressed the growth of a range of solid and liquid tumor cell types. Moreover, the combinations synergistically inhibited the growth of cells lines that were selected either in vivo or in vitro for Dpep resistance. Finally, we tested the combination of Dpep with ABT-263 in a mouse melanoma xenograft model. The combination more effectively inhibited tumor growth than either agent alone and, in contrast to vehicle or ABT-263, produced a 40% durable survival rate. Taken together, these observations highlight potential drug partners for the therapeutic development of Dpep. Full article

Thoracic malignancies are uniquely positioned for the integration of emerging technologies such as artificial intelligence (AI), which have the potential to advance precision oncology across the cancer care continuum. In cancer screening, AI has emerged as a promising strategy to enhance diagnostic accuracy, efficiency, and scalability. Deep learning applied to pathology (pathomics) and imaging (radiomics) has enabled the development of novel, noninvasive tools capable of predicting histologic and molecular features that may correlate with treatment response or toxicity. In drug discovery, computational approaches can analyze large-scale genomic, chemical, and clinical datasets to accelerate target identification and match candidate compounds to available targets; this may be particularly useful in the context of resistance to targeted therapy. AI tools may also support treatment planning for radiation and surgery, guide systemic therapy selection, and facilitate continuous monitoring for early identification of treatment resistance or toxicity. As these technologies are integrated into clinical workflows, careful attention to ethical, regulatory, and clinical governance frameworks will be essential to ensure equitable implementation and bias mitigation. Maintaining human oversight and a human-centered approach remain critical, as complex treatment decisions and sensitive patient interactions are central to the care of patients with thoracic malignancies. Full article

Objectives: Lymphedema (LE) is a debilitating complication in breast cancer patients, typically identified through clinical symptoms and volume-based diagnostics. As early diagnosis is crucial for favorable outcomes of microsurgical procedures, a more sensitive tool for LE assessment is required. The primary aim of this study was to evaluate whether a prolongation in postoperative indocyanine (ICG) lymphography drainage time, relative to preoperative baseline values, serves as a predictor of future LE development. Methods: A total of 41 women undergoing axillary lymph node dissection received ICG lymphography preoperatively and four weeks postoperatively. Drainage time (the duration for ICG to reach the axilla) was recorded. Clinical LE was defined as a >10% limb volume difference 12 months post-surgery, while subjective LE (sLE) was assessed via the Lymphedema Life Impact Score. Results: LE developed in 19.5% of patients. Patients who developed LE exhibited significantly higher mean drainage prolongation compared to those who did not (335 s vs. 40 s; p = 0.004). ROC analysis identified an optimal threshold of 119 s for predicting LE, yielding 100% sensitivity and 84.85% specificity (AUC = 0.96). sLE was reported by 48.8% of patients. Their drainage prolongation was significantly greater than in the sLE group (188 s vs. 13 s; p = 0.03). Conclusions: Preliminary findings suggest postoperative prolongation of ICG drainage time may serve as a potential predictor of future LE. In our cohort, a 119 s delay at four weeks post-operation was associated with LE at 12 months. While these results are promising, further research in larger, more diverse populations is required to validate these thresholds for clinical utility. Full article

Advanced gastric (GAC) or gastroesophageal junction (GEJAC) adenocarcinoma continues to carry a poor prognosis. Understanding GAC/GEJAC at the molecular level has provided a new understanding and the basis for individualized approaches to treatment. The current biomarker-driven therapy focuses on four areas: microsatellite instability (MSI), human epidermal growth factor receptor-2 (HER2), programmed death ligand-1 (PD-L1) combined positive score, and claudin 18.2 (CLDN18.2). However, because of improving technology, the focus has shifted to cancer cell-surface proteins and peptides. Each of these GAC/GEJAC subgroups provides a different treatment pathway. The agents utilized to treat advanced GAC/GEJAC include immune checkpoint inhibitors (ICIs), chemotherapy, monoclonal antibodies (mAbs), and antibody–drug conjugate (ADC) therapy, as well as bispecific antibodies (BsAbs), but they are certainly not limited to the above. Drug development has shifted in recent years to establish different mechanisms that are attempting more sophisticated and targeted approaches, such as BsAbs and ADCs. Meanwhile, the development of cytotoxics has tapered off. Along with these developments in drug therapy, more therapies directed at CLDN18.2, HER2, MSI, EGFR, HER3 and trophoblast cell-surface antigen 2 (TROP2) are underway. Here we review future areas in advanced GAC, including zanidatamab’s potential role in HER2-positive advanced GAC and deciphering the abundance of anti-CLDN18.2, extending beyond investigative therapies. Full article

Nuclear factor kappa B (NF-κB) signaling plays a central role in inflammation, immunity, cell survival, and cancer progression. Its constitutive activation is frequently observed in breast cancer, contributing to tumor growth, treatment resistance, and metastasis. MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and may modulate NF-κB signaling in a subtype-specific or -independent manner. The aim of the study was to identify miRNAs that may potentially regulate the activity of genes associated with NF-κB signaling across five molecular subtypes of breast cancer in Polish women. Tumor and matched normal tissue samples were collected from 405 patients with five breast cancer subtypes: luminal A (n = 130), HER2-negative luminal B (n = 100), HER2-positive luminal B (n = 96), non-luminal HER2-positive (n = 36), and triple-negative breast cancer (TNBC, n = 43). Expression profile of selected NF-κB-related genes were evaluated using mRNA microarrays and RT-qPCR. Protein levels were assessed by ELISA. Candidate regulatory miRNAs were identified via miRNA microarrays and validated using the miRDB database. A consistent upregulation of MAP3K7, TAB2, TNFAIP3, CSNK2A1, BCL2L1, XIAP, CXCL2, and PLAU was observed across all subtypes, suggesting activation of canonical NF-κB signaling. Downregulation of specific miRNAs, miR-1297 and miR-30a (targeting MAP3K7), miR-134 (TAB2), miR-125b (TNFAIP3), and miR-4329 (XIAP), may contribute to this deregulation. For CSNK2A1, BCL2L1, CXCL2, and PLAU, no regulatory miRNAs meeting our criteria were identified. Our study reveals a subtype-independent activation of the canonical NF-κB signaling pathway in breast cancer, underpinned by consistent upregulation of key components (at both the transcript and protein levels. Dysregulation of specific miRNAs likely contributes to this altered gene expression. These findings suggest the presence of a common NF-κB-driven oncogenic program across molecular subtypes, with potential implications for developing miRNA-based therapeutic strategies targeting inflammation, survival signaling, and treatment resistance in breast cancer. Full article

Background: Carbonic Anhydrases (CAs) represent regulators of cell adaptation to hypoxia, pH regulation, and metabolic fitness. Among cancers, multiple myeloma (MM) is a plasma cell malignancy sustained by hypoxia-driven metabolic adaptation, extracellular acidification, and redox imbalance. Tight regulation of tumor extracellular pH, mediated by Carbonic Anhydrases IX and XII, is crucial for myeloma survival, progression, and stemness, making these isoforms attractive therapeutic targets. Methods: We designed and synthesized a library of terpenoid-based hybrids by derivatizing chlorothymol and 4-isopropyl-3-methylphenol with either the natural coumarin umbelliferon or the 2,2′-dipicolylamine (DPA) scaffold. This chemical strategy aimed to selectively inhibit tumor-associated CAs IX/XII through coumarin- or DPA-mediated recognition, while terpenoid fragments were introduced to enhance lipophilicity, membrane permeability, and potential redox-modulating properties. The compounds were tested by a Stopped-Flow assay for CA inhibition, in cell-based assays for antiproliferative properties and by means of several antioxidant assays. Results: The most active compounds, connecting the coumarin core to a terpenoid tail, inhibited the targeted CAs in the nanomolar range, showing up higher selectivity over off-target isoforms (I and II). In studies performed on MM cell lines, selected derivatives reduced viability (IC₅₀ = 15.8–85.4 µM) and displayed favorable selectivity over normal cells. In silico investigations suggested that the compounds were able to interact selectively with the target enzymes. Conclusions: Collectively, these results support a dual-targeting strategy in which selective inhibition of tumor-associated CAs, combined with redox modulation, interferes with adaptive mechanisms of MM cells, providing a rational framework for the development of multifunctional agents against metabolically resilient hematological malignancies. Full article