Search Results (1,041)

Introduction: Intensive chemotherapy protocols and hematopoietic stem cell transplantation (HSCT) in children with cancer frequently lead to severe complications, such as mucositis and immune dysfunction. A growing body of evidence indicates that these complications are closely associated with the patient’s nutritional status and the composition of the gut microbiome, which becomes profoundly destabilized as a result of cytotoxic therapy and antibiotic use. Background: The aim of this review is to critically evaluate the current state of knowledge on the interplay between gut dysbiosis, metabolomic profiles—with particular emphasis on short-chain fatty acids (SCFAs)—and treatment-related toxicity in pediatric patients, as well as to delineate pathways toward personalized nutritional therapy. Methods: A narrative review was conducted, including clinical and preclinical studies published between January 2015 and October 2025. PubMed/MEDLINE, Embase, Cochrane Library, and other databases were searched, focusing on changes in microbiome composition, correlations between gut-derived metabolites and the severity of complications (sepsis, graft-versus-host disease [GvHD], mucositis), and the effects of targeted nutritional interventions (probiotics, prebiotics, postbiotics, and fecal microbiota transplantation [FMT]) on microbiome modulation during anticancer therapy. Results: The analysis demonstrates that pediatric oncologic treatment leads to a marked reduction in microbial diversity, including the loss of protective Clostridiales taxa (e.g., Faecalibacterium), accompanied by an overgrowth of Proteobacteria pathobionts. Metabolomic profiling indicates that low SCFA levels (e.g., butyrate < 20–50 µmol/g) are a strong predictor of severe mucositis, prolonged neutropenia, and an increased risk of sepsis. Interventions aimed at restoring eubiosis and enhancing SCFA production show potential in strengthening the intestinal barrier, modulating immune responses, and enabling maintenance of the planned relative dose intensity (RDI) of chemotherapy by reducing treatment-related toxicity. Conclusions: Gut microbiome profiling and fecal metabolomics represent promising prognostic tools in pediatric oncology. There is an urgent need for further research employing “omics”-based approaches to develop precise, individually tailored nutritional protocols. Such strategies, including postbiotics and FMT, may minimize treatment-related adverse effects and improve long-term clinical outcomes in pediatric patients. Full article

Background: The growing recognition of shared molecular pathways and molecular signatures between cardiovascular diseases and cancer has motivated interest in exploring antihypertensive-associated chemical space for oncological applications. Concurrently, artificial intelligence (AI)-driven molecular generation has enabled the rapid creation of virtual lead candidates for specific therapeutic indications, although their broader biological interaction profiles often remain unexplored. Methods: In this paper, we explore the computational screening of a library of AI-generated antihypertensive virtual lead compounds to evaluate their polypharmacological anticancer potential. The compounds were originally designed and prioritized for modulating $\mathsf{\beta }$-adrenergic receptors but are here re-evaluated in a cancer-focused context using a multi-stage in silico approach. We chose five (5) known cancer target proteins and performed compound profiling for drug-likeness, pharmacokinetic suitability, and safety. Docking simulations, binding free energy estimates, molecular interaction mapping, and pharmacophore modeling were used to evaluate the molecules’ interactions with the cancer-linked protein targets. We employed the binding free energy estimates of the ligand–protein complexes to determine compounds with polypharmacological anticancer potential. In addition, molecular dynamics simulations of some of the compounds with polypharmacological anticancer potential were employed to evaluate binding stability and dynamic behavior of selected ligand–target complexes. Results: Several compounds showed good docking scores, physicochemical characteristics, and pharmacokinetic profiles. Also, the results reveal that several AI-generated antihypertensive virtual leads exhibit favorable multi-target binding profiles, with consistent docking affinities and stable interaction networks across multiple cancer-related targets. Conclusions: Our findings suggest that several of the hypothetically evaluated compounds exhibit favorable physicochemical properties, acceptable predicted pharmacokinetic and safety profiles, and consistent predicted binding affinities across multiple cancer-relevant targets. Full article

Nanoparticles are widely explored in oncology as delivery platforms for cytotoxic drugs and molecularly defined therapeutic agents, including immunomodulators. While advances in nanomaterial engineering have enabled precise control over physicochemical properties, biological responses to nanoparticles remain difficult to predict and often diverge across experimental systems. Recent omics studies reveal that nanoparticle exposure induces coordinated cellular programs that extend beyond overt toxicity and are strongly shaped by delivery context, cellular state, and microenvironmental conditions. Importantly, these responses cannot be attributed solely to the payload, as nanocarriers themselves frequently engage stress, metabolic, and immune-related pathways, giving rise to non-additive and context-dependent effects. This Perspective proposes omics-based functional fingerprinting as a conceptual framework to interpret nanoparticle biology in cancer. Functional fingerprints are defined as integrated biological response states arising from nanocarrier–payload systems and resolving through transcriptomic, proteomic, metabolomic, and emerging single-cell or spatial approaches. By explicitly distinguishing carrier-dependent, payload-induced, and composite response programs, functional fingerprinting provides a means to reconcile heterogeneous observations and move beyond material-centered classification. Incorporating biological resolution and context awareness into nanoparticle profiling is expected to improve mechanistic interpretation, safety assessment, and the rational design of more predictive nanomedicine strategies. Full article

Despite significant advances in oncology, current cancer therapies remain constrained by toxicity, resistance, and limited selectivity. Endophytic fungi symbiotic microorganisms inhabiting plant tissues represent a sustainable and underexplored source of structurally diverse anticancer metabolites. These include alkaloids, terpenoids, polyketides, and peptides that disrupt microtubule dynamics, interfere with DNA replication, and induce mitochondrial-mediated apoptosis. They also modulate key oncogenic signalling pathways such as nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), thereby enhancing the efficacy of existing chemotherapies. Endophyte derived compounds further inhibit angiogenesis, suppress metastasis, and stimulate immune responses, offering multi-target mechanisms with reduced toxicity. This review examines strategies that enhance the discovery and yield of these bioactive metabolites, including One Strain Many Compounds (OSMAC), microbial co-culture, epigenetic activation, genome mining, and synthetic biology. A comparative assessment of endophyte-derived versus conventional anticancer agents highlights their potential for scalable, eco-sustainable production. Collectively, endophytic fungi are positioned as promising contributors to the next generation of accessible, cost-effective, and environmentally responsible anticancer therapies. Full article

Breast cancer represents a paradigmatic model of precision oncology, with treatment strategies increasingly guided by molecular profiling and biomarker-driven targeted therapies. Despite these advances in biological personalization, clinical outcomes remain strongly influenced by psychological and psychiatric factors that are still insufficiently integrated into oncological decision-making. This gap underscores the need for a broader, person-centered model of personalization that extends beyond tumor biology. This narrative review synthesizes current evidence on contemporary personalized strategies in breast cancer management, with a specific focus on the integration of precision oncology and psycho-oncology. A structured literature search was conducted across major biomedical databases to identify studies addressing molecular stratification, targeted treatments, psychiatric comorbidity, psychological profiles, and psycho-oncological interventions relevant to treatment personalization. While molecular classification and biomarker-guided therapies have substantially improved breast cancer outcomes, high rates of depression, anxiety, psychological distress, and maladaptive coping styles are consistently reported across disease stages. These psychological and psychiatric dimensions significantly influence treatment adherence, tolerability, quality of life, and ultimately clinical outcomes. Growing evidence supports the systematic use of psychological screening tools and tailored psycho-oncological interventions, both psychological and pharmacological, as integral components of personalized cancer care. Integrated care models combining oncological and psycho-oncological expertise are associated with improved patient-reported outcomes and may enhance overall therapeutic effectiveness. True personalization in breast cancer treatment extends beyond biological precision and requires the structured integration of psycho-oncological assessment and intervention into routine clinical pathways. Bridging precision oncology and psycho-oncology enables a more comprehensive, patient-centered approach, optimizing adherence, quality of life, and long-term outcomes. Future strategies should prioritize multidisciplinary models of care and the development of integrated clinical frameworks to achieve genuinely personalized breast cancer management. Full article

Domestic cats are among the most popular companion animals worldwide, with steadily increasing ownership and life expectancy. Paradoxically, despite their high prevalence and shared environmental exposures with humans, cats remain markedly underrepresented in molecular oncology research. Cancer is a leading cause of feline mortality, and alimentary lymphoma (AL) has emerged as one of the most common feline malignancies, yet its molecular landscape remains poorly characterized. This review summarizes current knowledge on feline AL, including epidemiology, risk factors, classification schemes, diagnostic challenges, treatment outcomes, and survival, with particular emphasis on low-grade alimentary lymphoma (LGAL), the most prevalent subtype. We discuss the complex relationship between chronic inflammatory enteropathies and lymphoma, highlighting diagnostic ambiguities and the inflammatory–neoplastic continuum. Importantly, we provide a critical overview of existing genomic, transcriptomic, epigenomic, proteomic, and metabolomic studies in feline AL, revealing a striking paucity of high-throughput, multi-omics analyses based on clinical material. Recent advances in feline genome assembly and annotation offer new opportunities to address these gaps. Furthermore, we compare feline AL with its human gastrointestinal T-cell lymphoma counterparts, demonstrating substantial molecular homology across key oncogenic pathways, including JAK/STAT signaling. This comparative perspective underscores the potential of feline AL as a naturally occurring model for the human disease. We conclude that comprehensive molecular characterization of feline AL is urgently needed to improve diagnostics, prognostication, and targeted therapies, with likely translational benefits for both veterinary and human oncology. Aim: The goal of this review is to summarize the current knowledge on feline alimentary lymphoma, including its origin, risk, classification, treatment approaches, and especially molecular landscape, which still remains poorly investigated with modern high-throughput techniques. Full article

Tankyrases (TNKS1 and TNKS2) are multifunctional enzymes of the poly(ADP-ribose) polymerase (PARP) family that regulate cellular homeostasis by catalyzing poly(ADP-ribosyl)ation and stabilizing protein–protein interactions through their ankyrin repeat clusters. By engaging with diverse sets of proteins, TNKSs act as central hubs that coordinate signaling and metabolic pathways. In this review, we discuss how TNKS –protein interactions underpin their roles across multiple biological pathways, including Wnt/β-catenin, YAP and SRC signaling, mTORC1 signaling, DNA damage repair (via PARP crosstalk and recruitment of repair factors), telomere maintenance, cell-cycle regulation, glucose metabolism, cytoskeleton rearrangement, autophagy, proteasomal degradation, and apoptosis. We highlight the structural basis of these interactions, emphasizing ankyrin repeat domain recognition motifs and the consequences of TNKS-mediated PARylation on protein stability and localization. By integrating findings from oncology, virology, and metabolism, we illustrate how TNKS functions as a nodal regulator linking genome stability, signaling fidelity, and metabolic control. The interplay between TNKS and these varied pathways is essential for the well-being of the organism, with its dysregulation having severe biological and clinical consequences, which are discussed here. Finally, we consider therapeutic implications of disrupting TNKS–protein interactions, with particular attention paid to selective small-molecule inhibitors and their translational potential in cancer, viral infections, and degenerative diseases. Full article

Melanoma is a malignant neoplasm that originates from melanocytes. It continues to pose a significant challenge in oncology due to its aggressive nature and limited treatment options. This study investigates the potential additive effects of PHEC-66, a cannabis extract, in combination with conventional chemotherapeutic agents auranofin, docetaxel, and cisplatin on the viability of a range of melanoma cell lines. These combinations were evaluated using the MTT assay on MM418-C1, MM329, C32, and D24 melanoma cells. There was a nuanced response observed when PHEC-66 was combined with docetaxel and auranofin in these cells, suggesting a potential additive effect. Contrastingly, the combination of PHEC-66 with cisplatin elicited an antagonistic effect, wherein the expected cytotoxicity of this drug was compromised. This unexpected interaction may stem from complex interplays between the agents that influence drug uptake, DNA damage response, and cell survival pathways. These findings underscore the importance of careful selection and assessment of drug combinations, as an additive effect and antagonistic interactions can significantly impact therapeutic outcomes. Further studies are warranted to elucidate the molecular mechanisms behind these interactions and to validate these observations using in vivo models. Full article

Gynecologic cancer is a major global health burden, and improvements in screening, surgical techniques, and systemic therapies have significantly prolonged survival. As a result, cardiopulmonary disease has emerged as a leading non-cancer cause of morbidity and mortality among gynecologic cancer survivors. Obesity, which is highly prevalent in this population, substantially increases cardiopulmonary risk by contributing to metabolic syndrome, cardiovascular disease, chronic inflammation, and reduced cardiopulmonary reserve. This narrative review summarizes current evidence on the epidemiology, pathophysiological mechanisms, and clinical spectrum of cardiopulmonary complications in obese patients with gynecologic malignancy. We review the contribution of obesity-related metabolic and endothelial dysfunction, cancer-associated hypercoagulability, and treatment-related toxicities, with particular emphasis on complications arising from surgery, chemotherapy, and radiotherapy. Epidemiologic data demonstrate a markedly increased burden of cardiovascular and pulmonary disease in obese gynecologic cancer patients, including higher rates of myocardial injury, heart failure, venous thromboembolism, and postoperative respiratory complications. Surgical treatment, although central to oncologic management, imposes substantial cardiopulmonary stress, placing obese patients at heightened perioperative risk. Future studies should focus on preoperative risk stratification, optimization of obesity-related comorbidities, and multidisciplinary perioperative management, including enhanced recovery pathways, as well as appropriate use of high-dependency or intensive care monitoring to reduce morbidity and improve both oncologic and long-term non-oncologic outcomes in this population. Full article

Background/Objectives: Human-driven environmental change can promote cancer development in wild species, yet the pathophysiology of wildlife cancers remain largely unexplored. Urogenital carcinoma (UGC) in the California sea lion (CSL) (Zalophus californianus) is one of the most common cancer types documented in any wild mammal. The pathogenesis of UGC in CSLs is known to be multifactorial, with links to environmental contaminant exposure and infection by Otarine Herpesvirus-1 (OtHV-1); however, the genomic features of these cancers have not been thoroughly explored. Understanding UGC pathogenesis in the CSL has important implications for the health of humans and other species that share environment and diet. Methods: We leveraged the evolutionary conservation between the domestic dog and CSL genomes to perform cross-species whole-exome sequencing (WES) of CSL UGC tumors and matched normal tissue pairs. We also used PCR and Sanger sequencing to investigate the prevalence of DNA from OtHV-1. Results: Bioinformatic analyses identified shared somatic variants and DNA copy number aberrations in UGC tumor samples, including recurrent exonic single-nucleotide variants in CD274/PD-L1, and recurrent copy number gains in CD274/PD-L1, TNFRSF14, CD200, CDK4, and PLCG2. In an extended cohort of 70 CSLs (tumor, matched normals, and controls), a recurrent C > T single-nucleotide variant in exon 4 of CD274/PD-L1 was identified in 54 of 68 (79.4%) CSLs with diagnosed UGC. OtHV-1 DNA was detected in 67 of 70 individuals (95.8%). Conclusions: These results demonstrate that cross-species exome capture provides a means to identify genomic alterations that may play a role in the molecular pathogenesis of UGC in the CSL and adds to the body of evidence for an association between OtHV-1 and UGC in this species. Full article

Pax6 is a multifunctional transcription factor that orchestrates cell cycle progression at distinct stages of early embryonic neurogenesis and serves as a molecular mediator integrating multiple signaling pathways associated with pathological processes. Within this framework, Pax6 is regarded as an attractive molecular target for developing new drugs aimed at combating neurodegeneration, oncology, and aniridia. The present review aims to examine published studies describing various Pax6-dependent molecular pathways to identify common principles and condition-specific differences in Pax6-regulated cascades in health and disease. These insights may contribute to the conceptual foundation for developing new therapeutic strategies targeting Pax6 as a molecular regulator. This review summarizes the data demonstrating a central role of Pax6 in governing the neuronal cell cycle in health and pathology. It is possible that Pax6 may act as a therapeutic target in certain pathophysiological conditions; however, the effectiveness of such a strategy will depend on the substrate chain in the signaling pathway, its branching, and the redundancy of mediators involved. Full article

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with poor patient outcomes. The long non-coding RNA NEAT1 (lncRNA NEAT1) has emerged as a critical driver of HNSCC pathogenesis. This review synthesizes current knowledge on lncRNA NEAT1’s aberrant expression, molecular mechanisms, and functional roles in HNSCC. LncRNA NEAT1 is significantly upregulated in tumors and promotes progression by acting as a competing endogenous RNA (ceRNA) for multiple miRNAs, such as miR-125b-5p, miR-204, and miR-34a-5p, thereby regulating downstream targets including SLC1A5, ZEB1, and components of the Wnt/β-catenin pathway. These interactions drive key oncogenic processes, including proliferation, metastasis, epithelial–mesenchymal transition, therapy resistance, and cell death inhibition. Clinically, high lncRNA NEAT1 expression correlates with advanced T stage, lymph node metastasis, and reduced survival, underscoring its potential as a diagnostic and prognostic biomarker. Therapeutically, emerging approaches such as nanoparticle-mediated delivery of siRNA/shRNA offer a promising strategy to target lncRNA NEAT1, potentially synergizing with existing immunotherapies. Although clinical translation remains challenging, lncRNA NEAT1 represents a highly promising biological target for future precision oncology in HNSCC. Full article

Background: Molecular subtyping of breast cancer usually relies on transcriptomic profiles, a method constrained by limitations in robustness and clinical applicability. While somatic point mutations represent a stable genomic alternative, their predictive utility is hindered by high dimensionality, extreme sparsity, and weak single-gene associations. Methods: Here, we present deepGene-BC, a deep learning framework that synergizes a pathway-informed feature selection strategy with a hybrid neural network tailored for sparse binary data. To distill sparse genome-wide mutations into a compact and interpretable feature set, deepGene-BC integrates mutation recurrence filtering, curated pathway priors, and mutual information-based gene prioritization. These refined features are subsequently modeled using a specialized hybrid architecture designed to capture complex linear effects, feature interactions, and higher-order nonlinear patterns. Results: When benchmarked against an independent test set (n = 273) from the TCGA breast cancer cohort, deepGene-BC achieved an overall accuracy of 77.3% and an average sensitivity of 75.2%, accompanied by a strong overall discriminative performance (macro-averaged AU-ROC = 0.94, 95% CI: 0.92–0.96). Conclusions: By effectively combining biologically informed feature engineering with deep learning, deepGene-BC holds significant promise for non-invasive molecular stratification and precision oncology. Full article

Radiotherapy has been a central component of cancer therapy for over a century, with the field rapidly evolving over time, resulting in improved outcomes. These advances have contributed to a changing demographic, with growing numbers of people living longer with, and surviving the disease. This has been accompanied by an increasing burden of chronic physical and psychological side effects, including radiotherapy-related toxicity. These long-term consequences have a substantial impact on patients, their carers, and healthcare systems. Significant global inequities persist, particularly in low- and middle-income countries (LMICs), where access to radiotherapy and comprehensive supportive and palliative care remains limited. Supportive oncology has emerged as a new field focusing on the management of acute, chronic, and emergent problems in people living with and beyond cancer. Despite its benefits, palliative radiotherapy continues to be underused, especially in specific patient groups including paediatrics, older age adults, and those with a short prognosis. Often treatment decisions in these patient groups are challenging and the integration of supportive oncology could help overcome this. Furthermore, radiotherapy toxicity and its management has been under-researched despite huge advancements in cancer treatments leading to a lack of guidelines and varied practice globally. Supportive oncology offers a framework to address these challenges through earlier integration into treatment pathways, multidisciplinary collaboration, and a stronger focus on symptom control, survivorship, and equity. Embedding supportive oncology within radiotherapy services is essential to delivering high-quality, patient-centred cancer care worldwide. Full article

The innate immune system’s core sensor, the NLRP3 inflammasome (Nucleotide-binding Oligomerization Domain, Leucine-rich Repeat, and Pyrin Domain-Containing Protein 3), is a pivotal multi-protein complex that detects cellular danger and microbial threats. While its activation is fundamental for host defense, chronic dysregulation of NLRP3 is a central driver of pathology in diverse diseases, ranging from neurodegeneration to cancer. This review comprehensively examines the complex and often paradoxical roles of the NLRP3 inflammasome in these two distinct domains. In neurodegenerative disorders, including Alzheimer’s and Parkinson’s, aberrant NLRP3 activation drives persistent neuroinflammation, leading to synaptic dysfunction and neuronal loss through the sustained release of mature IL-1β and IL-18. Conversely, NLRP3 exhibits a striking bimodal role in oncology; it can promote tumorigenesis by fueling chronic inflammation, metastasis, and immune evasion in certain tumor microenvironments, yet simultaneously enhances anti-tumor immunity and pyroptotic cell death in other specific contexts. This context-dependent function highlights a critical therapeutic challenge. We delineate the shared molecular pathways, contrast disease-specific outcomes, and the current landscape of therapeutic strategies aimed at modulating NLRP3. Understanding the nuanced role of the inflammasome offers novel insights into the convergence of chronic inflammation, neurodegeneration, and tumor biology, and holds promise for the development of targeted, context-dependent therapies with dual clinical applications. Full article