Search Results (579)

Non-small cell lung cancer (NSCLC) is a severe disease with a very poor prognosis. Some 30–80% of patients with NSCLC die within five years of cancer diagnosis. The main factors contributing to this condition are the lack of effective markers for diagnosing cancer at an early stage, as well as the complexity of the biological processes involved in tumorigenesis and progression. The development of knowledge regarding all aspects of NSCLC has provided information used in the detection, systemic anticancer therapy and monitoring of NSCLC, which has a significant impact on prognosis and quality of life. NSCLCs release various biological substances into the bloodstream. Liquid biopsies allow for the analysis of tumor components in body fluids, and the usefulness of these biopsy tests as a substitute for tumor tissue is increasing. In this article, we critically review the available literature on microRNAs, circulating cell-free DNA (cfDNA), tumor-educated platelets (TEPs), circulating tumor cells (CTCs), circulating extracellular vesicles (EVs), and metabolomic and proteomic markers in the diagnosis and monitoring of NSCLC. However, the usefulness of these new markers in clinical practice has significant limitations. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy marked by late diagnosis, rapid progression, and poor prognosis, with a 5-year survival rate of 2–9%. Traditional tissue biopsy faces limitations in accessibility and real-time monitoring. Liquid biopsy—a minimally invasive technique analyzing tumor-derived materials such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, tumor-educated platelets (TEPs), and cell-free RNAs (cfRNAs)—offers dynamic insights into PDAC biology. This review advances beyond the prior literature by offering a unified synthesis that bridges molecular mechanisms, biomarker dynamics, and clinical translation within the context of PDAC. It also summarizes key clinical trials evaluating liquid biopsy in PDAC, underscoring its growing impact on precision oncology. Full article

Non-coding RNAs (ncRNAs) are involved in many biological processes, making their identification and functional characterization a priority. Among them, long non-coding RNAs (lncRNAs) have been shown to regulate diverse cellular processes, such as cell development, stress response, and transcriptional regulation. The continued identification of new lncRNAs highlights the demand for reliable methods for their detection, with structural analysis offering insightful information. Currently, lncRNAs are identified using tools such as LncFinder, whose database has a large collection of lncRNAs from humans, mice, and chickens, among others. In this work, we present a graph-based algorithm to represent and compare RNA secondary structures. Rooted tree graphs were used to compare two groups of Saccharomyces cerevisiae RNA sequences, lncRNAs and not lncRNAs, by searching for structural similarities between each group. When applied to a novel candidate sequence dataset, the algorithm evaluated whether characteristic structures identified in known lncRNAs recurred. If so, the sequences were classified as likely lncRNAs. These results indicate that graph-based structural analysis offers a complementary methodology for identifying lncRNAs and may complement existing sequence-based tools such as lncFinder or PreLnc. Recent studies have shown that tumor cells can secrete lncRNAs into human biological fluids forming circulating lncRNAs which can be used as biomarkers for cancer. Our algorithm could be applied to identify novel lncRNAs with structural similarities to those associated with tumor malignancy. Full article

Background/Objectives: Glioblastoma (GBM), the most aggressive primary malignant brain tumor, has a dismal prognosis and limited treatment options. The dried rhizome of Ligusticum chuanxiong Hort. (Chuanxiong, CX) is a traditional Chinese medicinal herb frequently prescribed in formulas intended to invigorate blood circulation. CX also exhibits anti-glioma activity, but its molecular mechanisms remain incompletely understood. Methods: In this study, we combined transcriptomics and Raman spectroscopy to investigate the effects of reconstituted CX-dispensing granules (hereafter referred to as CXG solution) on U87MG cells, suggesting their dual role in promoting cell death and modulating collagen deposition and lipid metabolism. Results: Mechanistically, we demonstrated that the CXG solution downregulates hsa-miR-10a-5p, which directly targets BCL2L11, known to induce pro-apoptotic effects, as validated by qPCR and dual-luciferase reporter assays. Furthermore, the CXG solution and hsa-miR-10a-5p suppress lipid metabolism through a coherent feed-forward loop via targeting transcription factors SREBF1 and E2F1. An electrophoretic mobility shift assay (EMSA) confirmed E2F1 binds to the hsa-miR-29a promoter, leading to the synergistic repression of hsa-miR-29a-3p by SREBF1 and E2F1. Network pharmacology analysis combined with molecular docking suggested that the ferulic acid and adenosine in CX potentially modulate EGFR-the E2F1-hsa-miR-10a-5p axis. Conclusions: These findings elucidate CX’s multi-target anti-GBM mechanisms and propose a novel therapeutic strategy combining metabolic intervention with miRNA-targeted therapy, providing novel insights into feed-forward loop regulation in miRNA networks. Full article

Cervical cancer (CC) is the fourth most common cancer among women globally, with venous thromboembolism (VTE) representing a life-threatening complication. Cancer-associated thrombosis (CAT) arises from tumor-driven activation of hemostasis, worsening prognosis. Recently, circulating microRNAs (miRNAs) have emerged as potential biomarkers for both CAT and cervical tumorigenesis. Thus, this study aimed to assess the implications of five miRNAs—miR-20a-5p, -23a-3p, -125b-5p, -145-5p, and -616-3p—in CC-related VTE context. These miRNAs were quantified by RT-qPCR in plasma from 69 CC patients before treatment. Briefly, VTE occurred in nine patients, decreasing overall survival (OS) [log-rank test, p = 0.005; hazard ratio (HR) = 4.78; 95% confidence interval (CI), 1.42–16.05]. Lower miR-20a-5p levels predicted VTE (ꭓ² test, p = 0.027) and, in subgroup analyses, they were linked to cervical squamous cell carcinoma (CSCC) and older age (ꭓ² test, p = 0.003 and p = 0.043, respectively). In VTE patients, miR-145-5p downregulation was associated with improved OS (log-rank test, p = 0.018), an effect also observed in the adenocarcinoma (ADC) subgroup (log-rank test, p = 0.039). The remaining miRNAs showed subtype-specific links to clinicopathological features and survival. These findings highlight the potential value of circulating miRNAs in thrombotic risk and prognosis assessment in CC. Full article

HPV-related head and neck cancers are increasing globally and although they constitute a major public health problem, there are currently no validated screening or early detection methods in widespread clinical use. This review discusses advances in clinical and molecular aspects of prevention, screening, and early detection of HPV-related head and neck cancers (HNCs), such as potential use of HPV blood or saliva seropositivity, RNA biomarkers, liquid biopsy, circulating tumor DNA, and proteomics. In addition to HPV vaccination, public education about vaccination, smoking, and safe sexual practices is warranted. Continued research is warranted to define optimal use and integration of approaches for prevention, screening, and early detection methods of HNCs. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality globally, largely due to delayed diagnosis in its early stages. While conventional diagnostic tools like low-dose CT and tissue biopsy are routinely used, they suffer from limitations including invasiveness, radiation exposure, cost, and limited sensitivity for early-stage detection. Liquid biopsy, a minimally invasive alternative that captures circulating tumor-derived biomarkers such as ctDNA, cfRNA, and exosomes from body fluids, offers promising diagnostic potential—yet its sensitivity in early disease remains suboptimal. Recent advances in Artificial Intelligence (AI) and radiomics are poised to bridge this gap. Objective: This review aims to explore how AI, in combination with radiomics, enhances the diagnostic capabilities of liquid biopsy for early detection of lung cancer and facilitates personalized monitoring strategies. Content Overview: We begin by outlining the molecular heterogeneity of lung cancer, emphasizing the need for earlier, more accurate detection strategies. The discussion then transitions into liquid biopsy and its key analytes, followed by an in-depth overview of AI techniques—including machine learning (e.g., SVMs, Random Forest) and deep learning models (e.g., CNNs, RNNs, GANs)—that enable robust pattern recognition across multi-omics datasets. The role of radiomics, which quantitatively extracts spatial and morphological features from imaging modalities such as CT and PET, is explored in conjunction with AI to provide an integrative, multimodal approach. This convergence supports the broader vision of precision medicine by integrating omics data, imaging, and electronic health records. Discussion: The synergy between AI, liquid biopsy, and radiomics signifies a shift from traditional diagnostics toward dynamic, patient-specific decision-making. Radiomics contributes spatial information, while AI improves pattern detection and predictive modeling. Despite these advancements, challenges remain—including data standardization, limited annotated datasets, the interpretability of deep learning models, and ethical considerations. A push toward rigorous validation and multimodal AI frameworks is necessary to facilitate clinical adoption. Conclusion: The integration of AI with liquid biopsy and radiomics holds transformative potential for early lung cancer detection. This non-invasive, scalable, and individualized diagnostic paradigm could significantly reduce lung cancer mortality through timely and targeted interventions. As technology and regulatory pathways mature, collaborative research is crucial to standardize methodologies and translate this innovation into routine clinical practice. Full article

Biliary tract diseases, including both benign and malignant conditions such as cholangitis, cholelithiasis, primary sclerosing cholangitis, cholangiocarcinoma, and gallbladder cancer, present significant challenges for timely diagnosis and effective clinical management. Conventional diagnostic approaches, which primarily rely on imaging and standard laboratory tests, often lack the sensitivity and specificity needed for early detection, accurate risk stratification, and personalized treatment planning. In recent years, advancements in point-of-care (POC) diagnostic technologies, along with the identification and validation of novel biomarkers, have begun to reshape the diagnostic landscape. This review provides a comprehensive overview of the clinical utility and limitations of current POC tests and biomarkers, ranging from well-established markers such as carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) to emerging molecular indicators such as circulating microRNAs and circulating tumor DNA. We examine their applications across acute management, chronic disease monitoring, and cancer detection; identify existing gaps in diagnostic practice; and discuss strategies for incorporating these tools into standard clinical workflows to enhance patient outcomes. Full article

Background/Objectives: This study explores the potential of the inducible G protein-coupled kinin B1 receptor (B1R) as a target for the diagnosis and treatment of prostate cancer (PCa) and aims to develop the first theranostic agent targeting hB1R for both molecular imaging and radionuclide therapy. Methods: B1R expression was analyzed via qPCR and immunohistochemistry in human PCa cells and tissues specimens. A novel ⁶⁴Cu/NOTA-conjugated peptide analog of the potent B1R antagonist R954 was synthetized and evaluated in vitro and in vivo. Results: B1R was confirmed to be expressed (RNA, protein) by varying degrees in all PCa cell lines and tissues investigated, with protein level significantly correlating with tumor grades. This finding was supported by similar analyses from the TCGA and MSKCC databases. In vitro, the ⁶⁴Cu/NOTA-βAla-R954 conjugate showed nanomolar affinity/potency at hB1R, complete plasma stability over 24 h, significant cellular uptake (up to 33% of ID at 24 h), and dose-dependent anti-clonal growth effects. In vivo, the radioconjugate remained stable in circulation for up to 90 min and was primarily excreted intact via the kidneys following IV administration. Intravenous ⁶⁴Cu/NOTA-βAla-R954 (7.5 MBq) effectively detected subcutaneous PCa xenografts via µPET imaging in male athymic nude mice. At a single higher dose (65 MBq; 50 µg/kg), it significantly reduced tumor growth without observable toxicity. This antitumor effect was associated with increased apoptosis (active caspase-3) and reduced proliferation (Ki67), as shown by immunohistochemistry. In contrast, the nonradioactive ^NatCu/NOTA-βAla-R954 had no therapeutic effect at the same dose. Conclusions: Our findings provide proof-of-concept for the potential theranostic use of ⁶⁴Cu/NOTA-R954 in PCa, and potentially other types of B1R-positive solid cancers. Full article

Background: Intermittent fasting (IF) is emerging as a promising non-pharmacological intervention in oncology, with the potential to modulate key biological processes including metabolic reprogramming, inflammation, autophagy, and immune function, particularly through the PI3K/AKT/mTOR pathway. However, translating IF into clinical practice requires robust tools to monitor its biological impact and therapeutic effectiveness. Objective: This narrative review aims to present and critically evaluate current diagnostic and monitoring strategies that can support the safe and effective integration of IF into oncological care. Methods: A comprehensive literature search was conducted across PubMed/Medline, Science Direct, Scopus, Wiley Online Library, and Google Scholar using a combination of free-text and MeSH terms related to intermittent fasting, oncology, biomarkers, immunophenotyping, metabolic pathways, gut microbiome, and diagnostic imaging. Results: Two principal categories of monitoring objectives were identified. The first—mechanistic monitoring—focuses on elucidating IF-induced biological effects, including modulation of insulin/IGF-1 signaling, oxidative stress reduction, autophagy activation, immune reprogramming, and microbiome alterations. Advanced research tools such as single-cell RNA sequencing, proteomics, metabolomics, and circulating tumor DNA (ctDNA) assays offer high-resolution insights but currently remain limited to preclinical or translational settings due to cost and complexity. The second—clinical response monitoring—assesses IF’s impact on treatment outcomes, including chemotherapy and immunotherapy response, toxicity reduction, tumor dynamics, and maintenance of nutritional and functional status. This requires clinically validated, accessible, and interpretable diagnostic tools. Conclusions: A dual-layered monitoring framework that integrates both mechanistic insights and clinical applicability is essential for the personalized implementation of IF in oncology. Although preliminary findings are promising, large-scale randomized trials with standardized protocols are necessary to confirm the efficacy, safety, and feasibility of IF in routine oncological care. The integration of IF with modern diagnostics may ultimately contribute to a more individualized, biologically informed cancer treatment paradigm. Full article

Background/Objectives: MiRNAs have demonstrated promising roles in the diagnosis of pancreatic cancer and in the prognostic assessment of affected patients. Methods: We conducted a prospective pilot study including 23 patients diagnosed with advanced-stage pancreatic cancer and 10 healthy controls, matched by age and sex. In the screening phase, we evaluated the expression of 176 miRNAs in pooled plasma samples from both groups using real-time PCR. Subsequently, we validated the overexpression of selected miRNAs in individual plasma samples using the same technique. Statistical analysis was performed using IBM SPSS Statistics version 29. Results: During the screening phase, 22 miRNAs exhibited differential expression in patients with pancreatic cancer compared to healthy controls. Among these, hsa-miR-100-5p (27.8-fold increase), hsa-miR-122-5p (7.5-fold), hsa-miR-885-5p (7.2-fold), hsa-miR-34a-5p (5.7-fold), and hsa-miR-193a-5p (4.4-fold) showed the most pronounced upregulation. In the validation phase, all five candidates demonstrated significant overexpression in individual plasma samples (p < 0.001). Their circulating levels also showed associations with tumor stage (p < 0.05). Conclusions: Our findings highlight a distinct circulating miRNA signature associated with advanced pancreatic cancer, supporting the potential role of hsa-miR-100-5p, hsa-miR-122-5p, hsa-miR-885-5p, hsa-miR-34a-5p, and hsa-miR-193a-5p as minimally invasive biomarkers for disease detection and staging. Larger, multicenter studies including early-stage patients and disease control groups will be required to validate these biomarkers and determine their clinical utility. Full article

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, in part due to late diagnosis and limited prognostic tools. In recent years, microRNAs, small, non-coding regulators of gene expression, have emerged as key modulators of tumor metabolism, microenvironmental crosstalk, and therapeutic response in HCC. This narrative review synthesizes evidence published from January 2000 through April 2025, focusing on four interrelated themes: (1) miRNA-driven metabolic rewiring; (2) circulating and exosomal miRNAs as diagnostic and (3) predictive biomarkers; (4) miRNA-based therapeutic strategies. We conducted a targeted PubMed search using terms related to HCC, miRNA biology, biomarkers, metabolism, and therapy, supplemented by manual reference mining. Preclinical and clinical studies reveal that loss of tumor-suppressor miRNAs and gain of oncomiRs orchestrate glycolysis, lipid and glutamine metabolism, and stromal-immune remodeling. Circulating miRNA signatures, including single- and multimarker panels, demonstrate diagnostic AUCs up to 0.99 for early-stage HCC and distinguish HCC from cirrhosis more accurately than alpha-fetoprotein. Predictively, miRNAs such as miR-21 and miR-486-3p correlate with sorafenib resistance, while tissue and exosomal miRNAs forecast recurrence and survival after curative therapy. Therapeutic manipulation, restoring tumor-suppressor miRNAs via mimics or AAV vectors and inhibiting oncomiRs with antagomirs or LNA oligonucleotides, yields potent anti-tumor effects in models, affecting cell cycle, apoptosis, angiogenesis, and immune activation. Despite technical and delivery challenges, early-phase trials validate target engagement and inform safety optimization. In this review, we highlight opportunities to integrate miRNA biomarkers into surveillance algorithms and combine miRNA therapeutics with existing modalities, charting a roadmap toward precision-guided management of HCC. Full article

Cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) are aggressive malignancies with limited therapeutic options and poor prognoses. In recent years, microRNAs (miRNAs) have gained attention as key molecular regulators involved in tumor progression, chemoresistance, and metastasis. This review explores the diagnostic, prognostic, and therapeutic potential of miRNAs in CCA and PDAC, emphasizing their shared and distinct molecular pathways and their utility in the context of precision oncology. Several dysregulated miRNAs, most notably miR-21 and miR-155, are overexpressed in both cancers and contribute to activation of oncogenic pathways such as PI3K/AKT signaling, epithelial–mesenchymal transition, and inflammatory cascades. miR-21, in particular, is associated with resistance to gemcitabine and cisplatin. In contrast, tumor-suppressive miRNAs such as miR-34a and miR-145 are often downregulated, and their restoration using synthetic mimics has demonstrated promising antitumor effects in preclinical studies. Moreover, circulating miRNAs show potential as non-invasive biomarkers for early detection and disease monitoring. Advanced delivery platforms, including nanoparticles and exosome-based systems, are being developed to improve the stability and tumor specificity of miRNA-based therapeutics. miRNAs represent a promising class of molecules in the diagnosis, stratification, and treatment of CCA and PDAC. Their dual role as biomarkers and therapeutic agents positions them at the intersection of molecular pathology and personalized medicine. Further multicenter clinical trials and mechanistic studies are needed to validate their clinical applicability and to refine delivery strategies for targeted miRNA modulation. Full article

Under physiological and pathological conditions, all cells release extracellular vesicles named exosomes, which act as transporters of lipidic, protein, and genetic material from parent to recipient cells. Neoplastic cells can secrete higher number of exosomes to exert pro-tumoral effects such as microenvironmental changes, disease progression, immunosuppression and drug-resistance. This holds true for both organ-specific cancers and hematologic malignancies. One of the most important components of exosomal cargo are microRNAs which can mediate all the abovementioned effects. More specifically, microRNAs are small non-coding RNAs, routinely detected through quantitative real-time PCR, which act as translational suppressors by regulating protein-coding genes. Considering their high stability in all body fluids and viability in circulation, research is currently focusing on this type of RNAs for the so called “liquid biopsy”, a non-invasive tool for disease diagnosis and longitudinal monitoring. However, several issues remain to be solved including the lack of standardized protocols for exosome isolation and miRNA detection. Starting with this premise, our review aims to provide a wide description of the known microRNA panels employed in the prominent hematological malignancies, which will hopefully redefine the approach to these very challenging diseases in the near future. Full article

Epidermal growth factor receptor (EGFR) inhibitors remain a cornerstone in the treatment of metastatic colorectal cancer with RAS and BRAF wild-type cancer. Yet, primary and acquired resistance limit their benefit for many patients. A growing body of evidence reveals that resistance is not random but rather driven by a complex network of molecular alterations that sustain tumor growth independent of EGFR signaling. These include amplification of ERBB2 (HER2) and MET, activation of the PI3K and AKT pathways, EGFR extracellular domain mutations, and rare kinase fusions. The concept of negative hyperselection has emerged as a powerful strategy to refine patient selection by excluding tumors with these resistance drivers. Multiple clinical trials have consistently shown that patients who are hyperselected based on comprehensive molecular profiling achieve significantly higher response rates and improved survival compared to those selected by RAS and BRAF status alone. Liquid biopsy through circulating tumor DNA has further transformed this landscape, offering a noninvasive tool to capture tumor heterogeneity, monitor clonal evolution in real time, and guide rechallenge strategies after resistance emerges. Together, negative hyperselection, ctDNA-guided monitoring, and emerging therapeutics define a precision-oncology framework for identifying, tracking, and overcoming resistance to anti-EGFR therapy in mCRC, moving the field toward more effective and individualized care. Looking ahead, the development of innovative therapeutics such as bispecific antibodies, antibody drug conjugates, and RNA-based therapies promises to further expand in this challenging clinical scenario. These advances move precision oncology in colorectal cancer from concept to clinical reality, reshaping the standard of care through molecular insights. Full article