Search Results (1,209)

Chronic periodontitis has emerged as a potential modifiable risk factor for several tumors, yet its role remains underexplored beyond epidemiological associations. This perspective review examines the immunological and molecular interplay between periodontitis and various cancers—including prostate, colorectal, oral squamous cell carcinoma, and oral potentially malignant disorders—highlighting shared inflammatory mediators and immune dysregulation. Special attention is given to immune cell profiles, cytokine expression, dysbiosis, and common miRNA signatures. Recent evidence suggests that periodontitis may act not only as a co-factor in tumor development but also, in some contexts, as a marker of therapeutic response, particularly in patients undergoing immune checkpoint inhibitor therapy. In our view, future research should prioritize mechanistic studies to define common immune–inflammatory pathways and clarify whether periodontitis functions as a field cancerization process or as a facilitator of malignant transformation in already compromised tissues. The relationship between cancer and periodontitis underscores the need to integrate oral health into oncologic care and immunotherapy management. Full article

Objective: Non-oncological musculoskeletal chronic pain has a high prevalence and is a cause of disability, reduced quality of life, and significant economic impact. Physical exercise is presented as a treatment option; however, pain measurement remains a challenge, and various biomarkers are potential candidates to objectify this process. This systematic review aims to study the effect of physical exercise on non-oncological musculoskeletal chronic pain and its associated biomarkers based on randomized controlled trials. Methods: A search for randomized controlled trials was conducted in the PubMed, Web of Science, and Scopus databases based on the established inclusion and exclusion criteria, along with a risk of bias assessment following the recommendations of the Cochrane Collaboration. Results: Five studies investigated various physical exercise interventions and their effects on biomarkers linked to chronic pain. Exercise consistently reduced self-reported pain, though no clear overall correlation with biomarker changes was found. However, significant associations emerged for specific biomarkers, particularly inflammatory markers and those identified through structural and functional brain imaging, suggesting potential mechanisms underlying pain modulation. Conclusions: The findings suggest that identifying chronic pain variations through biomarkers requires selecting markers linked to immune activity or brain processes. More randomized controlled trials with sufficient sample sizes and rigorous methodologies are needed. Despite this, physical exercise remains a valuable intervention for managing non-oncological musculoskeletal chronic pain. Additionally, it holds potential as a tool for uncovering novel biomarkers that may contribute to the objectification and understanding of chronic pain mechanisms. Full article

Malignant neoplasms, like non-small cell lung cancer (NSCLC), remain a major global health challenge. Lung cancer is the leading cause of cancer-related deaths worldwide, with over two million new cases and 1.8 million deaths annually. NSCLC accounts for approximately 85% of cases, underscoring its substantial public health impact. Advances in molecular biology have driven the development of new therapies beyond traditional treatments. Among them, mRNA-based immunoadjuvant therapies, like cancer vaccines, have emerged as promising utilities in NSCLC by triggering targeted immune responses. The aim of this paper is to review ongoing and completed studies on mRNA vaccines in NSCLC. The efficacy of mRNA vaccines in NSCLC relies on the identification of immunogenic tumor-specific antigens, frequently derived from genomic profiling databases. Completed clinical trials have assessed the safety and potential benefit of selected mRNA vaccines—such as CV9202—administered alone or in combination with radiotherapy or tyrosine kinase inhibitors. Ongoing studies are exploring the therapeutic potential of mRNA-based approaches targeting defined molecular alterations in NSCLC, particularly in conjunction with Programmed Death-Ligand 1 (PD-L1) immune checkpoint inhibitors to enhance antitumor immune responses. mRNA vaccines have emerged as a promising therapeutic option for NSCLC, with the potential to enhance immune responses and limit tumor progression, as demonstrated in ongoing clinical trials. They offer the possibility of personalized treatment with relatively few side effects. However, larger and long-term studies are required to fully confirm their safety and efficacy. Future research should aim to identify the most effective antigens, enhance stability, and refine delivery strategies to improve efficacy and personalization, while also addressing immune suppression within the tumor microenvironment. Full article

Immune dysregulation is being increasingly recognized as a leading sign of a wide spectrum of inborn errors of immunity (IEIs). Therefore, patients with IEIs are frequently managed in non-immunological settings, including hematology and oncology units, during the diagnostic process or follow-up. The most relevant hematological signs associated with IEIs comprise autoimmune cytopenia (AIC), lymphoproliferative diseases (LPD), malignancies, hemophagocytic lymphohystiocitosis (HLH), bone marrow failure (BMF), myelodysplastic syndromes (MDS), and peripheral or tissue eosinophilia. The prognosis of patients with IEIs can significantly improve when a molecular diagnosis is established, as it can allow the use of targeted treatments, guide appropriate follow-up strategies and, in some cases, support the rationale for hematopoietic stem cell transplantation or gene therapy. Therefore, there is an urgent need to recognize the warning signs suggestive for an underlying IEI among patients presenting with common hematological features and to ensure an appropriate diagnostic approach. As a general rule, clinicians should always provide a clinical alert in the presence of two or more IEI-associated hematological signs, as well as a positive familial history for IEI or hematologic immune dysregulation, a personal history of severe infections, and other signs of immune dysregulation. Concerning AIC, an increased likelihood of IEI is characteristic of patients with treatment refractoriness, autoimmune hemolytic anemia, or multilineage cytopenia. In the case of LPD, the main elements of suspicion are represented by the chronic or recurrent disease course, the persistence of Epstein–Barr Virus (EBV) infection, and the development of lymphoproliferation in atypical localizations. Among patients with malignancy, clinicians should investigate for IEI those with rare neoplasia, virus-associated tumors, and an association with syndromic features, while patients with HLH should always receive an immunological assessment when a clear rheumatologic trigger, underlying malignancy, or well-recognized cause is not evident. The case of MDS and BMF is complex, as new monogenic entities are continuously being described. However, it is pivotal to consider the presence of monocytopenia, warts, vasculitis, and neurological disease, as well as specific cytogenetic abnormalities, such as chromosome 7 monosomy, as warning sings for IEIs. Finally, the main red flags for IEIs in patients with eosinophilia are skeletal/facial abnormalities, recurrent abscesses, refractory eczema, organomegaly, or thrombocytopenia. Full article

The gut–brain axis refers to the bidirectional communication network linking the gut microbiota and the central nervous system (CNS). Recent research has highlighted the critical role of gut microbiota in influencing brain health, neurogenesis, and neuroinflammation. In the context of brain tumors, especially gliomas, the gut–brain axis plays a significant role in tumor development, progression, and response to therapy. Gut dysbiosis, characterized by an imbalance in microbiota composition, has been linked to chronic inflammation, immune suppression, and altered blood–brain barrier (BBB) permeability, key factors in glioma pathogenesis. Gut-derived metabolites such as short-chain fatty acids (SCFAs) and neurotransmitters can either promote or inhibit tumor growth, impacting the tumor microenvironment (TME) and immune responses. Emerging evidence suggests that microbiome modulation, through strategies such as probiotics, prebiotics, and dietary interventions, may enhance anti-tumor immunity and improve the efficacy of conventional treatments like chemotherapy, radiotherapy, and immunotherapy. This review examines the interactions between gut microbiota and brain tumors, focusing on how microbiota alterations may influence tumor biology and therapeutic outcomes. Understanding the mechanisms of the gut–brain axis could lead to novel adjunctive therapies in neuro-oncology, offering new prospects for personalized treatment strategies in brain tumor management. Full article

Background: Immunotherapy has revolutionized oncology care, but clinical response to immune checkpoint inhibitors (ICIs) remains unpredictable, and treatment carries substantial risks and costs. The EpiSwitch^® CiRT blood test is a novel 3D genomic assay that stratifies patients by probability of ICI benefit using a binary, blood-based classification: high (HPRR) or low (LPRR) probability of response. Methods: This interim analysis of the ongoing PROWES prospective real-world evidence study evaluates the clinical utility of CiRT in 205 patients with advanced solid tumors. The primary endpoint was treatment decision impact, assessed by pre-/post-test physician surveys. Secondary endpoints included treatment avoidance, time to ICI initiation, concordance with clinical response, early discontinuation rates, and exploratory health economic modeling. Longitudinal use, resistance monitoring, and equity analysis by social determinants of health (SDoH) were also explored. Results: CiRT results influenced clinical decision-making in a majority of cases. LPRR status was associated with higher rates of treatment avoidance and early discontinuation due to immune-related adverse events (IrAEs). In contrast, HPRR patients experienced greater clinical benefit and longer ICI exposure. CiRT classification was not associated with short-term imaging-based response outcomes, supporting its role as an independent predictor. Given that ICI therapy and supportive care can cost more than $850,000 per patient, CiRT offers potential value in avoiding ineffective treatment and associated toxicities. Conclusions: CiRT demonstrates meaningful clinical utility as a non-invasive, predictive tool for guiding immunotherapy decisions across tumor types. It enables more precise treatment selection, improves patient outcomes, and supports value-based cancer care. Full article

Background: Single-agent pembrolizumab represents a standard of care in the first-line treatment of patients with metastatic non-small cell lung cancer (mNSCLC) with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%. Real-world evidence is of increasing importance in oncology, as clinical trial inclusion criteria may not be truly reflective of the patient population seen in daily clinical practice. Methods: We performed a prospective–retrospective single-center study including 121 patients who received pembrolizumab as a first-line therapy for mNSCLC with a PD-L1 TPS ≥ 50%. Our aims were to make a comparison with published clinical trial results by assessing the efficacy and safety of pembrolizumab monotherapy in our population. We collected patient demographics, clinical characteristics of the disease, and treatment outcomes, including efficacy and safety. Results: A total of 121 patients were included, with a median follow-up of 40.77 months. The median progression-free survival in the real world (rwPFS) was 20.73 months (95% CI 12.24–29.22), and the median overall survival (OS) was 29.30 months (95% CI 16.57–42.04). Immune-mediated adverse events (irAEs) occurred in 42% of patients, with serious events (grade 3 or more) occurring in 12%. ECOG PS 2, male gender, squamous histology, pleural and visceral metastases, and treatment with corticosteroids prior to initiation of pembrolizumab were found to be negative predictors for overall survival, while the occurrence of irAEs was the predictor of longer survival. Conclusions: This study provides further real-world insights into the efficacy of pembrolizumab in a heterogeneous patient population with advanced NSCLC in a single center in Serbia. It also confirmed the value of good ECOS PS and the occurrence of irAEs as predictors of favorable outcomes. Full article

Background and Objectives: Metformin, a staple in diabetes care, has recently emerged as a candidate chemotherapeutic agent. In vitro studies suggest that metformin inhibits cancer growth by altering cellular metabolism and enhancing immune responses. Clinical observations further indicate that it suppresses key tumor-promoting pathways such as mTOR and STAT3. This review critically evaluates the therapeutic potential of metformin in oncology through the lens of precision medicine. This review integrates evidence from molecular mechanisms, clinical studies, biomarker-driven trial designs, and the regulatory challenges that continue to delay its approval for oncologic use. Methods: A structured literature search (2015–2025) identified 63 relevant studies, including preclinical, clinical, and translational research. Conclusions: Although metformin shows consistent anticancer effects in laboratory and animal models, its clinical benefits in patients are variable. This inconsistency is likely due to tumor heterogeneity and a lack of biomarker-based patient selection in trials. Targeting these shortcomings through biomarker-enriched, tumor-specific clinical trials is essential to define metformin’s role as a repurposed agent in precision oncology. Full article

Artemisinin and its derivatives are widely recognized for their exceptional antimalarial efficacy. Recently, accumulating evidence indicates therapeutic potential beyond malaria. Despite these advances, detailed mechanisms and pharmacological limitations remain incompletely defined. This review summarizes their pharmacological activities and molecular mechanisms associated with oncology, immunoregulation, and metabolic disorders. Mechanistically, these compounds exert potent antitumor effects by inducing oxidative stress, arresting the cell cycle, triggering apoptosis, and inhibiting angiogenesis. They likewise modulate immune responses, re-establishing immune homeostasis and enhancing the effectiveness of immunotherapeutic strategies. Preliminary evidence also suggests involvement in metabolic regulation, pointing to promising avenues for treating metabolic disorders. Given alternative mechanisms of artemisinin and its derivatives, we also discuss the trinity modulation network among antitumor activity, immunoregulation, and metabolic homeostasis. We anticipate that future research will address these knowledge gaps, thereby enhancing the clinical utility of artemisinin and its derivatives and improving patient outcomes across diverse pathologies. Full article

Cancer, a leading global cause of death responsible for nearly 10 million deaths annually, demands innovative therapeutic strategies. Intrinsic cytotoxicity and biocompatibility of zinc oxide nanoparticles (ZnO-NPs) have rendered them promising nanoplatforms in oncology. We herein systematically review their applications for targeted cancer chemotherapy, with a focus on physicochemical properties, drug delivery mechanisms, and interactions with the tumor microenvironment (TME). We searched PubMed, SCOPUS, and Web of Science from inception through December 2024 for peer-reviewed preclinical studies on cancer models. Results were qualitatively synthesized. Quality was assessed with the SYRCLE risk of bias tool. Among 20 eligible studies, ZnO-NPs were frequently functionalized with ligands to enhance tumor targeting and minimize systemic toxicity. Chemotherapeutic agents (doxorubicin, 5-fluorouracil, docetaxel, cisplatin, gemcitabine, and tirapazamine) were loaded into ZnO-based carriers, with improved anticancer efficacy compared to free drug formulations, particularly in multidrug-resistant cell lines and in vivo murine xenografts. The mildly acidic TME was exploited for pH-responsive drug release, premature leakage reduction, and improvement of intratumoral accumulation. Enhanced therapeutic outcomes were attributed to reactive oxygen species generation, zinc ion-mediated cytotoxicity, mitochondrial dysfunction, and efflux pump inhibition. Deep tumor penetration, apoptosis induction, and tumor growth suppression were also reported, with minimal toxicity to healthy tissues. ZnO-NPs might constitute a versatile and promising strategy for targeted cancer chemotherapy, offering synergistic anticancer effects and improved safety profiles. Future studies emphasizing long-term toxicity, immune responses, and scalable production could lead to clinical translation of ZnO-based nanomedicine in oncology. Full article

Background/Objectives: Cancer immunotherapy has revolutionized the field of oncology by harnessing the immune system to attack cancer cells, increasing survival in a broad spectrum of malignancies. However, despite its positive therapeutic benefit, immunotherapy is also associated with a spectrum of adverse events affecting various vital organs, including the cardiovascular system. Methods: We conducted a comprehensive review of the available literature on the epidemiology, pathophysiological mechanisms, and current management approaches for cardiovascular adverse events associated with cancer immunotherapy. In addition, we evaluated emerging personalized strategies and interventions aimed at mitigating these risks and improving patient outcomes. Results: Immunotherapy is associated with a broad spectrum of potentially serious cardiovascular adverse events, including immune-mediated myocarditis, heart failure, arrhythmias, pericarditis, and accelerated atherosclerosis. Among these, immune checkpoint inhibitor-associated myocarditis is the most well characterized and potentially fatal form of cardiotoxicity, with reported mortality rates approaching 50%. Similarly, chimeric antigen receptor T-cell therapy, despite its powerful antitumor efficacy, is frequently associated with cytokine release syndrome—a profound immune activation that can lead to significant systemic and cardiovascular complications. In response to these challenges, several personalized strategies are currently under development, including artificial intelligence and machine learning approaches, genetic and transcriptomic profiling, novel biomarker discovery, and integrated risk scoring systems, all aimed at enhancing risk stratification and improving patient care. Conclusions: Cancer immunotherapy has been associated with a range of immune-related cardiac adverse events, both non-severe and severe. As such, it is critically important to adopt a personalized approach to patient management before, during, and after the administration of immunotherapy. Early recognition through heightened clinical vigilance, along with the implementation of individualized risk assessment tools, is essential for identifying patients at high risk of immunotherapy-induced cardiotoxicity. These strategies are imperative for optimizing patient outcomes and ensuring safe and effective cancer treatment. Full article

Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a complex molecular landscape. Despite extensive research, our understanding of the molecular mechanisms remains incomplete, hindering the development of effective therapeutic strategies for this disease. Long non-coding RNAs (lncRNAs) have emerged as crucial factors in cancer biology, regulating key networks across various malignancies. These molecules exert their regulatory functions through interactions with nucleic acids or proteins, thereby influencing signaling pathways within tumor cells. Consequently, lncRNAs play a significant role in key processes like cell proliferation, metastasis, immune evasion, and treatment resistance. This review offers a comprehensive overview of current knowledge regarding lncRNA-mediated mechanisms in HNSCC. The first section explores how lncRNAs influence tumor processes through various modulation mechanisms, including transcriptional and post-transcriptional regulation, chromatin remodeling, and epigenetic modifications. We also highlight the impact of lncRNAs on specific signaling pathways that control essential cellular functions (e.g., proliferation, apoptosis, angiogenesis, invasion, metastasis). Ultimately, this underscores the promising potential of lncRNAs as diagnostic biomarkers and therapeutic targets capable of enhancing patient care in oncology. Gaining a deep understanding of how lncRNAs modulate carcinogenic mechanisms may yield innovative approaches for early detection, personalized treatment, and improved clinical outcomes for HNSCC patients. Full article

Despite improved diagnostic and treatment protocols, cancer remains a leading cause of morbidity and mortality globally. There are increasing rates of certain cancer types, including the highly drug-resistant colorectal cancer, in younger population cohorts. Therapeutic advances in oncology have led to the application of immunotherapy-based agents, including checkpoint inhibitors, antibodies, and adoptive cell therapies. Such immunotherapy approaches are greatly hindered by the tumour microenvironment and lack of specificity. Therapeutic vaccines are an innovative and rapidly advancing area of oncology, having potential for application as mono- and combined therapy in clinical settings, offering long term efficacy against disease recurrence. Advances in vaccine production using gene editing and bioprocessing techniques allows for novel vaccine types, including protein-based subunit vaccines, virus-like particle vaccines, and viral vector- and nucleic acid-based (RNA and DNA) vaccines. Cancer vaccines are designed to deliver specific tumour antigens, which activate anti-cancer cytotoxic T cells and helper T cells to produce immune memory, providing long term anti-cancer action. When coupled with advances in machine learning and artificial intelligence, anti-cancer vaccines may revolutionise oncology protocols and improve patient prognosis. This review aims to discuss current immunotherapy options in cancer treatment and recent advances in anti-cancer vaccine modalities. Full article

In vitro culture systems have advanced cancer biology, particularly through 2D and 3D tumor cultures. These have answered numerous scientific inquiries and propelled human oncologic research, with growing recognition of their potential to improve cancer treatment in companion animals, specifically cats and dogs. These species develop cancer spontaneously, closely resembling specific human cancer subtypes. For example, canine and feline mammary tumors are especially valuable for studying tumor biology. In vitro models from these tumors therefore offer a unique opportunity for veterinary cancer research. Recent 3D cell culture advancements provide promising platforms for predicting therapeutic responses in human cancer and may be applied to mammary tumors in animals. However, while limitations in fully recapitulating in vivo conditions and predicting chemotherapy response have been observed in colorectal tumoroids, similar challenges are emerging in mammary and breast tumors. In particular, canine mammary tumors and human breast cancers share critical heterogeneity and microenvironmental factors usually inadequately modeled in vitro. This review critically examines the predictivity of 3D mammary tumoroids from humans and companion animals, highlighting challenges related to stromal and immune cell preservation, reproducibility, and the translational gap between in vitro findings and clinical outcomes. We propose future directions to optimize these models for both comparative oncology and veterinary-specific applications. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) presents a formidable challenge in oncology due to its aggressive progression, propensity for early metastasis, and resistance to conventional therapies. The development of effective and less toxic treatments is crucial for improving the prognosis of PDAC. We aimed to investigate the synergistic antitumor potential of modified FOLFIRINOX (mFOLFIRINOX) combined with natural killer (NK) cell therapy in PDAC models. Methods: We evaluated changes in NK-cell-activating ligands and apoptosis-inducing receptor expression after mFOLFIRINOX treatment both in vitro and in vivo. Subsequently, NK cells were administered to mFOLFIRINOX-pre-treated PDAC cells to assess NK cell cytotoxicity, immune responses, and tumor progression both in vitro and in vivo mouse models. Results: Treatment with mFOLFIRINOX led to the significant upregulation of NK-cell-activating ligands and apoptosis-inducing receptors across the PDAC cell lines and tumor cells collected in vivo, thereby enhancing their susceptibility to NK-cell-mediated cytotoxicity. In comparison with either treatment alone, mFOLFIRINOX and NK cell combination therapy resulted in enhanced cytolysis in all cell lines. In vivo studies demonstrated that combination therapy substantially inhibited tumor growth and prolonged survival in a mouse model. Conclusions: mFOLFIRINOX combined with NK cell therapy demonstrates enhanced antitumor activity against PDAC, potentially improving clinical outcomes. These findings highlight the need for continued research to optimize this combination strategy for clinical utility. Full article