Search Results (6,981)

Lung cancer remains the leading cause of cancer-related mortality worldwide in both males and females. Despite recent advances in precision-targeted therapeutics, mortality rates remain high, largely due to delayed diagnoses when curative interventions are no longer feasible. Recent studies from our group demonstrated that the LINE-1 mRNA and associated miRNA cargo of plasma exosomes can be used as sensitive and specific diagnostic and prognostic biomarkers of non-small-cell lung cancer (NSCLC). Because exosomes from various cancer types can be detected in urine, we extended our investigation to examine these analytes in urine exosomes from NSCLC patients. LINE-1 ORF1 and ORF2 mRNA levels, along with miR-21-5p, miR-126-3p, miR-210-3p, miR-221-3p, Let-7b-5p, miR-146a-5p, miR-222-3p, miR-9-5p, and miR-1277-5p, were higher in urine exosomes from NSCLC patients compared to healthy controls. The cargo of urine-derived exosomes often mirrored that of plasma exosomes and correlated with several clinicopathologic characteristics. The strong predictive performance of urine exosomal RNAs distinguishing NSCLC patients from controls suggests these measurements may serve as a complementary and readily accessible source for noninvasive assessment of patients with NSCLC. Full article

Background/Objectives: Endocrine-disrupting chemicals (EDCs) interfere with hormonal homeostasis and have been implicated in gynecological malignancy pathogenesis. This narrative review synthesizes current evidence regarding EDC exposure and breast, endometrial, ovarian, and cervical cancers, examining molecular mechanisms, epidemiology, and diagnostic and clinical implications. Methods: We conducted a literature review using PubMed/MEDLINE, Embase, Scopus, and Cochrane databases through April 2026, including systematic reviews, meta-analyses, prospective cohorts, case-control studies, and mechanistic investigations examining EDC-cancer associations. Methodological quality was appraised using the Newcastle-Ottawa Scale and AMSTAR-2, with overall certainty of evidence rated using the GRADE framework. Results: Major EDC classes—bisphenol compounds, phthalates, polychlorinated biphenyls, organochlorine pesticides, and per- and polyfluoroalkyl substances—demonstrate carcinogenic potential through estrogen receptor modulation, epigenetic alterations, oxidative stress, and oncogenic signaling disruption. Breast cancer shows the strongest evidence, with prenatal and early-life DDT/DDE exposure associated with up to a 3.7-fold increased risk. Endometrial cancer demonstrates associations with xenoestrogen mixtures exhibiting non-monotonic dose-responses, whereas ovarian and cervical cancers show emerging but limited associations. Common mechanisms include receptor crosstalk, epigenetic dysregulation with transgenerational effects, oxidative genomic instability, metabolic reprogramming, and cancer stem cell enrichment. Conclusions: Evidence supports EDC contributions to gynecological malignancy through convergent pathways, though causal inference remains constrained by observational epidemiology, long latency periods, and challenges in characterizing real-world mixture exposures. Diagnostic and prevention strategies should integrate EDC exposure into risk-prediction models, leverage multi-omics biomarkers for early detection, and emphasize exposure reduction during critical developmental windows alongside regulatory reform. Full article

Unc-51-like kinase 3 (ULK3) is a key member of the ULK serine/threonine kinase family. Aberrant ULK3 expression has been increasingly linked to tumorigenesis and malignant progression in multiple cancer types. However, the precise role of ULK3 in tumor initiation and progression remains incompletely understood. Leveraging integrated multi-omics data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), we systematically characterized the expression of ULK3 at both the transcript and protein levels across 33 cancer types. We also evaluated genomic alterations, prognostic significance, alternative splicing, pathway enrichment, tumor stemness, immune infiltration, and immunotherapy-related biomarkers. In parallel, we investigated the function of ULK3 in prostate cancer PC-3 cells using cellular localization analysis, wound-healing assays, and MTT assays. We further applied Connectivity Map (CMap) screening and molecular docking to identify candidate ULK3 activators. ULK3 was significantly upregulated in 13 cancer types, including Bladder Urothelial Carcinoma, Breast Invasive Carcinoma, and Lung Adenocarcinoma. In contrast, ULK3 was downregulated in Cholangiocarcinoma and Head and Neck Squamous Cell Carcinoma. High ULK3 expression was associated with poor overall survival in Adrenocortical Carcinoma, Kidney Renal Clear Cell Carcinoma, and Skin Cutaneous Melanoma. Copy number amplification contributed to ULK3 overexpression. A recurrent A206V missense mutation was detected in the protein kinase (Pkinase) domain. Genes co-expressed with ULK3 were enriched in RNA splicing, methylation, oxidative phosphorylation, and energy metabolism. ULK3 expression showed positive correlations with tumor stemness indices and m1A/m5C/m6A RNA modification regulators. From an immunological perspective, high ULK3 expression was associated with lower Immune Score, increased M2 macrophage infiltration, and co-expression of PD-L1, CTLA4, and LAG3 in most cancers. ULK3 expression was also correlated with Tumor Mutational Burden in Kidney Renal Clear Cell Carcinoma and Rectum Adenocarcinoma. In addition, ULK3 expression was associated with Microsatellite Instability in Brain Lower Grade Glioma, Lung Adenocarcinoma, and Uterine Corpus Endometrial Carcinoma. ULK3 overexpression promoted proliferation and migration in PC-3 cells. Cephaeline was screened as a putative ULK3 activator. Overall, ULK3 expression and amplification were associated with poor clinical outcomes, tumor stemness, immunosuppression, and RNA dysregulation. These findings highlight the potential value of ULK3 as a pan-cancer diagnostic and prognostic biomarker and as a predictor of immunotherapy response, particularly in prostate cancer. Full article

Background: KRAS mutations are among the most common oncogenic drivers in non-small cell lung cancer (NSCLC) and are associated with substantial molecular and immunological heterogeneity. However, the clinicopathological associations and prognostic relevance of KRAS mutation subtypes and co-occurring genomic alterations in relation to PD-L1 expression and survival outcomes remain incompletely understood, particularly in the immunotherapy era. Methods: This retrospective single-center study included 93 KRAS-mutant NSCLC patients identified among 543 consecutively sequenced cases between March 2024 and March 2025. KRAS mutation subtypes, co-mutations involving TP53, STK11, and KEAP1, PD-L1 expression status, clinicopathological features, and survival outcomes were evaluated. Overall survival was assessed using Kaplan–Meier analysis and Cox proportional hazards regression models. Results: KRAS mutations were detected in 17.1% of NSCLC patients. G12C was the most frequent KRAS subtype (38.7%), followed by G12V (18.3%) and G12D (14.0%). Co-occurring mutations were identified in 73.1% of cases, most commonly involving TP53 (40.9%) and STK11 (33.3%). PD-L1 expression was negative in 48.4% of patients, low in 28.0%, and high in 23.7%. No significant association was identified between KRAS mutation subtype and PD-L1 expression (p = 0.663). STK11-mutated tumors demonstrated a trend toward lower PD-L1 expression levels compared with STK11 wild-type tumors. However, none of the molecular variables retained independent prognostic significance. Immunotherapy was associated with significantly prolonged overall survival (median OS: 24 vs. 7 months, p = 0.013) and remained independently associated with improved survival in multivariate analysis (HR: 0.376, 95% CI: 0.204–0.694, p = 0.002). Advanced-stage disease independently predicted worse survival outcomes (HR: 13.43, 95% CI: 1.81–99.79, p = 0.011). Conclusions: KRAS mutation subtypes and co-occurring genomic alterations demonstrated limited independent prognostic significance in this real-world NSCLC cohort. In contrast, immunotherapy was associated with improved overall survival in this retrospective cohort. These findings should be interpreted as observational and hypothesis-generating rather than evidence of predictive treatment benefit. Larger prospective studies integrating genomic and immune biomarkers are warranted. Full article

Background/Objectives: Anaplastic lymphoma kinase (ALK) fusion is a driver gene translocation detected in 3–5% of patients with non-small-cell lung cancer (NSCLC). Next-generation sequencing (NGS)-based tests are the standard of care for detecting actionable gene alterations; however, false negatives remain a concern. Immunohistochemical staining is another reliable, rapid, and low-cost method for detecting ALK fusions. Previous studies have reported high concordance with NGS, although further studies are needed to draw definitive conclusions. Methods: A retrospective analysis was conducted on consecutive patients with NSCLC who were tested using the Oncomine Dx Target Test (ODxTT), an amplicon-based DNA and RNA NGS test for NSCLC, and ALK-immunohistochemistry (IHC) at our institution between 8 August 2019 and 11 April 2025. Results: Of 919 eligible patients included in this study, ALK fusion was detected in 30 (3.26%) patients, whereas ALK-IHC was positive in 35 (3.80%) patients. The concordance and κ coefficient of the two tests were 99.4% and 0.920, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ALK-IHC for ODxTT were 100%, 99.4%, 85.7%, and 100%, respectively. Five discordant patients were NGS negative and IHC positive. Among the five discordant cases, one had a false-negative NGS result, whereas the remaining four had false-positive ALK-IHC results, including three patients with neuroendocrine carcinomas. Conclusions: ALK-IHC shows diagnostic accuracy comparable to ODxTT, although prudent interpretation is needed for patients without adenocarcinoma. Our findings suggest the complementary role of ALK-IHC alongside NGS-based testing, particularly in patients with a high pre-test probability of harbouring ALK fusions. Full article

Backgrounds: Bladder cancer shows pronounced biological heterogeneity that underlies its variable clinical course and prognosis. Our study aims to delineate clinically relevant differences in bladder cancer using an immunohistochemistry-based molecular subtyping approach. Methods: This retrospective study included 590 patients with bladder cancer treated at a single center. Tumors were stratified into luminal versus non-luminal categories according to CK20, GATA3, CK5/6, and CK14. Associations between molecular subtype, histopathological growth patterns, pathological response to neoadjuvant chemotherapy (NAC), and clinical survival endpoints were analyzed. Overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) were evaluated through Kaplan–Meier survival curves together with Cox proportional hazards regression analyses. Results: Non-luminal tumors exhibited significantly more aggressive pathological growth patterns, including higher levels of tumor budding (p = 0.002), a predominance of non-cohesive or spindle/single-cell architecture (p = 0.003), and more frequent disseminated spreading patterns (p = 0.001), whereas luminal tumors more commonly displayed a higher frequency of tertiary lymphoid structures (TLSs; p = 0.041). Among patients receiving NAC, non-luminal tumors achieved a significantly higher pathological complete response (pCR) rate compared with luminal tumors (p = 0.007), while no significant inter-subtype difference was detected in pathological downstaging between subtypes (p = 0.126). Despite inferior pathological response, luminal tumors demonstrated significantly improved OS (p = 0.003), RFS (p = 0.002) and PFS (p < 0.001) compared with non-luminal tumors. In multivariable Cox regression analysis, molecular subtype was identified as an independent predictor of OS, with luminal tumors showing a lower mortality risk (HR = 0.51, 95% CI 0.33–0.79, p = 0.003). Conclusions: These findings indicate that pathological response and long-term survival follow distinct, subtype-dependent trajectories in bladder cancer. Favorable pathological response does not necessarily correspond to improved long-term survival across molecular subtypes. Full article

Circulating tumor DNA (ctDNA) was initially conceived as a minimally invasive surrogate for interrogating cancer biology; however, three decades of evidence have demonstrated that plasma is not a passive reservoir of tumor-derived material, but rather a dynamic and biologically heterogeneous milieu in which multiple competing genomic signals coexist. This review explores the level of interpretive rigor required to translate ctDNA detection into clinically actionable precision oncology. Clonal hematopoiesis of indeterminate potential (CHIP) is discussed not as an occasional confounder, but as an intrinsic source of biological background noise, underscoring the critical importance of matched leukocyte sequencing to discriminate tumor-derived alterations from hematopoietic variants, particularly in older individuals and in patients previously exposed to cytotoxic therapies. The widespread assumption that variant allele frequency (VAF) directly reflects tumor burden is critically re-evaluated through the mathematical relationships linking VAF to tumor fraction, local copy-number architecture, and mutation multiplicity. Within this framework, estimation of cancer cell fraction (CCF) and probabilistic discrimination between clonal and subclonal events are examined, including the emergence of reversion mutations as molecular evidence of therapy-driven evolutionary adaptation. The review also addresses the central paradox of ultra-sensitive sequencing technologies: although unique molecular identifiers and duplex sequencing can extend analytical sensitivity below 0.01% VAF, sensitivity in the absence of contextual specificity risks conflating technical artifacts and biologically insignificant alterations with clinically meaningful disease. Equal emphasis is placed on pre-analytical variables, highlighting how sample collection, stabilization, and processing protocols define the upper limit of downstream analytical reliability. Beyond single-nucleotide variants, fragmentomic and methylation-based approaches are presented as complementary orthogonal dimensions capable of revealing tumor-associated signals even when mutational evidence is limited or absent. Longitudinal ctDNA assessment is argued to provide substantially greater biological and clinical insight than isolated static measurements, while robust clinical reporting is shown to depend on transparent disclosure of assay limitations, residual uncertainty related to CHIP, and structured bidirectional communication between molecular laboratories and treating clinicians. Ultimately, the transition from a biomarker-centered model toward an integrated systems-based framework, combining genomics, epigenomics, fragmentomics, and evolutionary modeling, emerges as the defining challenge for the next generation of liquid biopsy in precision oncology. Full article

Squamous cell lung cancer (SqCLC) accounts for 20–30% of non-small cell lung cancer (NSCLC) and remains associated with a poorer prognosis compared with adenocarcinoma. Despite advances in treatment, 5-year overall survival for advanced (stage IV) disease remains below 10–15%. Unlike non-squamous NSCLC, SqCLC is characterized by a high tumor mutational burden and complex genomic landscape dominated by alterations in tumor suppressor genes and lineage survival pathways including TP53, CDKN2A, PIK3CA, FGFR1, SOX2, and the NFE2L2/KEAP1 oxidative stress pathway, as well as dysregulation of the NOTCH signaling pathway, but it harbors relatively few actionable oncogenic drivers, resulting in limited treatments for targeted therapy. HER2 alterations can occur by multiple mechanisms, including activating mutations, gene amplifications, and protein overexpression. They comprise a very small percentage of NSCLC, with HER2 mutations reported in approximately 1–3% and HER2 amplifications observed roughly in 2–4%. While HER2 alterations are well characterized in lung adenocarcinoma, the prevalence, genomic context, and clinical significance of HER2 alterations in SqCLC remain incompletely defined. Advances in next-generation sequencing have led to improved ability to detect HER2 alterations and facilitated the development of HER2 targeted therapies. Available treatments for advanced/metastatic SqCLC have been historically limited to platinum-doublet chemotherapy, with immune checkpoint inhibitors such as anti-PD-1/PD-L1 newly emerging in the past decade. Selective HER2 tyrosine kinase inhibitors and HER2 antibody/drug conjugates have shown improved efficacy in HER2-altered NSCLC as shown in DESTINY-LUNG02 and BEAMION LUNG-1 trials; however, most of the enrolled patients had non-squamous histology, with minimal or no SqCLC-specific efficacy data reported. Future progress in HER2-altered SqCLC will require inclusion of SqCLC in HER2 basket trials, incorporation of comprehensive molecular profiling and standardized HER2 testing in squamous histology. This review summarizes the current state of knowledge of HER2 biology in SqCLC and highlights areas for future directions for precision oncology in SqCLC. Full article

Background and Objectives: A subset of cancer patients treated with immune checkpoint inhibitors may experience rapid tumor progression rather than therapeutic benefit, a phenomenon described as hyperprogressive disease (HPD), which is linked to poor prognosis and shortened survival. Reliable biomarkers capable of predicting HPD remain lacking. To better understand the molecular background of HPD, we analyzed promoter region methylation and somatic mutation profiles in cancer-related genes in patients with malignant melanoma (MM) and renal cell carcinoma (RCC) undergoing anti-PD-1/PD-L1 treatment. Methods: Patients diagnosed with MM or RCC and treated with anti-PD-1/PD-L1 agents between 2011 and 2020 were included, and FFPE tumor samples along with paired normal tissues were analyzed. A diagnosis of HPD was assigned to patients with RECIST 1.1-defined progressive disease who demonstrated a ≥2-fold acceleration in tumor growth kinetics after initiation of immune checkpoint inhibitor therapy. Methylation-specific real-time PCR was performed on 54 samples (15 MM tumors, 22 RCC tumors, 17 RCC-matched adjacent normal samples) to assess promoter methylation of PIK3CA, BAP1, PTEN, and TP53. Next-generation sequencing (NGS) with an 86-gene pan-cancer panel was conducted on 9 HPD samples. Results: Promoter hypermethylation involving PIK3CA, BAP1, PTEN, and TP53 was more pronounced in HPD-associated tumor samples (n = 16) than in tumors without HPD (n = 21). Within the MM cohort, PTEN and TP53 methylation levels demonstrated statistically significant differences between the two groups (p = 0.005 and p = 0.028, respectively), while no comparable associations were observed in RCC patients. NGS analysis detected missense mutations classified as pathogenic or likely pathogenic in 5 of 9 HPD patients (55.6%), involving KIT, PTEN, and VHL. Conclusions: Promoter region hypermethylation in cancer-related genes may contribute to the aggressive tumor behavior observed in HPD. The somatic variants identified in HPD patients are consistent with known oncogenic pathways. These findings support further investigation of epigenetic and genomic biomarkers for HPD risk stratification in larger, prospective cohorts. Full article

In this study, a new series of (E)-4-((2-(2-(4-amino-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)acetyl)hydrazono)methyl)phenyl 4-halogenobenzenesulfonates (3a–3d), where 3a = F, 3b = Cl, 3c = Br, and 3d = I, were successfully synthesized via a straightforward synthetic route. The structures of the obtained compounds were fully characterized and confirmed by spectroscopic techniques, including FT-IR, ¹H NMR, and ¹³C NMR, as well as LC-MS/MS analysis. 1,2,4-triazole-based hydrazone derivatives (3a–3d) were investigated using IR and NMR spectroscopy and DFT calculations. Intermolecular interactions, HOMO-LUMO, dipole moment, polarization, first-order hyperpolarizability, and molecular electrostatic potential studies on the molecules were examined. The HOMO and LUMO energy gap study supports the charge transfer probability in the molecules. These were conducted to investigate the reactivity and stability of heterocyclic molecules in bioactivity analysis. Electron density mapping within the molecular electrostatic potential plot and electrostatic potential representation within the iso-surface plot evaluated the concept of charge distribution in the molecule as nucleophilic reactions and electrophilic regions. The predicted nonlinear optical (NLO) properties of the molecules are much greater than those of urea. The results obtained from these investigations collectively provide evidence that the molecules possess nonlinear optical applications. Novel triazole–hydrazone-functionalized aryl sulfonate derivatives (3a–3d) were evaluated for their anticancer potential against a panel of brain and non-brain cancer cell lines. Compound 3b exhibited the most favorable overall biological profile, displaying potent activity against SH-SY5Y neuroblastoma (GI = 7.59 μM) and U87MG glioblastoma cells (GI = 13.85 μM), together with the lowest toxicity toward normal FL fibroblasts (GI = 62.02 μM). Compounds 3c and 3d demonstrated remarkable potency against IDHmut-U87 glioma cells (GI = 3.87 and 3.27 μM, respectively), although their selectivity toward cancer cells was limited. DNA degradation studies revealed substantial fragmentation, particularly in C6 and SH-SY5Y cells, while migration assays indicated reduced cellular motility. Molecular docking studies identified compound 3b as the strongest PI3Kα binder, supporting a possible. In addition, the antimicrobial activities of compounds 3a–3d were evaluated against selected Gram-positive and Gram-negative bacteria as well as Candida species using the broth microdilution method. The compounds exhibited measurable antimicrobial effects with MIC values ranging from 156 to 625 µg/mL, showing moderate growth inhibition against the tested microorganisms. Although the observed activity was lower than that of the reference antimicrobial agents, the results indicate that these triazole–hydrazone derivatives possess a detectable level of antimicrobial activity and provide a basis for further structural optimization. Collectively, the results suggest that compound 3b represents the most promising lead structure due to its balanced combination of potency, selectivity, and predicted target engagement. Molecular docking was performed to evaluate the binding potential of newly synthesized triazole derivatives (3a–3d) against PI3Kα. The docking protocol was validated by re-docking alpelisib, yielding an RMSD of 0.64 Å. Among the tested compounds, 3b showed the most favorable binding energy (−9.94 kcal/mol) and estimated Ki value (52.13 nM), consistent with its superior in vitro activity. Its interactions with key PI3Kα residues, including Val851, Ser854, Met922, and Asp933, support a stable binding mode within the ATP-binding pocket. In silico ADME and toxicity analyses suggested acceptable drug-likeness characteristics, absence of major hepatotoxic, mutagenic, and carcinogenic liabilities, and moderate predicted acute toxicity profiles. These findings suggest that 3b is the most promising derivative for further validation. Full article

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide despite advances in diagnosis and treatment. Increasing evidence suggests that alterations in the lung microbiome may contribute to NSCLC development and progression; however, findings remain inconsistent due to heterogeneous biological materials and methodological differences among studies. Therefore, this study aimed to characterize the lung tissue microbiome in NSCLC using a paired tissue-based approach. Methods: Thirty-two patients with NSCLC were enrolled. For each patient, two samples were collected: primary tumor tissue and matched macroscopically unchanged adjacent lung tissue. The V3-V4 region of the 16S rRNA gene was amplified and sequenced, followed by bioinformatic analysis using the QIIME2 pipeline. Results: Tumor tissues demonstrated lower alpha (Shannon H = 9.60, q = 0.001) and beta (Jaccard pseudo-F = 1.26, q = 0.015) diversity compared with adjacent controls, indicating reduced microbial complexity within the tumor microenvironment. Escherichia-Shigella was the most abundant detected genus (~12%) in both groups, although without a statistically significant difference. Analysis of microbiome variation in relation to spatial distance between sampled tissues revealed a strong trend toward significance (p = 0.07) with a substantial effect size (R² = 0.207). Conclusions: The observed microbiome alterations in NSCLC were more evident at the ecological level than in overall taxonomic composition, supporting a model of microbial community simplification rather than complete compositional replacement. Our findings also suggest that tumor-adjacent lung tissue may not represent a fully neutral control due to the local field effect. The relatively high abundance of Escherichia-Shigella indicates that this taxon may warrant further investigation in NSCLC microbiome studies. Full article

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, mainly due to metastasis. Circulating tumor cells (CTCs) act as the biological “seeds” of dissemination, traveling through the bloodstream to colonize distant organs. However, the blood is a hostile environment where CTCs must constantly face immune pressure. This review explores the bidirectional interactions between CTCs and immune cells in CRC, asking whether CTCs are merely vulnerable targets of immunosurveillance or can exploit the immune system for survival and metastasis. We dissect intrinsic and extrinsic immune evasion mechanisms, including MHC-I modulation, immune checkpoint expression (PD-L1, CD47, FasL), platelet cloaking, and neutrophil extracellular traps (NETs). Furthermore, we examine how CTCs form heterotypic clusters with monocytes, neutrophils, and lymphocytes, creating pro-metastatic niches and promoting phenotypic plasticity. The impact of CTCs on systemic immunity, including reprogramming of NK cells, T lymphocytes, and myeloid-derived suppressor cells (MDSCs), is discussed. Importantly, we highlight the emerging role of CTCs as dynamic biomarkers for immunotherapy, focusing on the predictive value of PD-L1+ CTCs and the potential of CTC-derived neoantigens for personalized vaccination. Despite progress, challenges remain in standardization, detection sensitivity, and clinical validation. Understanding the equilibrium between immune elimination and evasion by CTCs is crucial to develop novel interventions that interrupt the metastatic dialog and improve outcomes for CRC patients. Full article

Background/Objectives: Oral cavity squamous cell carcinoma (OSCC) remains a major global health burden, with outcomes strongly dependent on stage at diagnosis. Although the oral cavity is directly accessible to clinical examination, many cases are still detected at advanced stages. This narrative review aimed to summarize current trends in OSCC diagnosis and early monitoring, with emphasis on non-invasive and minimally invasive techniques and biomarkers. Methods: A semi-systematic narrative literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science using predefined combinations of OSCC-, early-detection-, imaging-, cytology-, liquid-biopsy-, salivaomics-, artificial-intelligence-, and biosensor-related terms. English-language systematic reviews, meta-analyses, reviews of reviews, translational studies, and clinically relevant original articles were prioritized, with explicit attention to oral cavity-specific evidence and clearly identified extrapolation from broader head-and-neck or oropharyngeal cancer settings. Results: Conventional oral examination and histopathological assessment of biopsy specimens remain the diagnostic foundation. Adjunctive methods may support lesion triage, biopsy-site selection, risk stratification, and early monitoring, but cannot replace tissue diagnosis. Narrow-band imaging, optical coherence tomography, and molecular brush cytology appear particularly promising for specialist assessment and surveillance. Liquid biopsy and saliva-based biomarker platforms offer translational potential, particularly for repeatable monitoring, but clinical implementation is limited by methodological heterogeneity, pre-analytical variability, inconsistent thresholds, and insufficient external validation. Artificial intelligence and biosensor platforms remain promising but largely developmental. Conclusions: Progress in early OSCC diagnosis and monitoring will most likely depend on integrated diagnostic models combining clinical examination, adjunctive imaging, minimally invasive sampling, molecular biomarkers, and computational decision-support tools, validated in prospective multicenter studies. Full article

Background: Hepatocellular carcinoma (HCC) is one of the most common and deadliest cancers worldwide. Alpha-fetoprotein (AFP), a widely used and accessible tumoral marker, has limited performance in the early detection of HCC among high-risk populations. This study aims to evaluate the potential added value of ccfDNA (circulating cell-free DNA) fragment size, alone or in a multiparameter panel, using accessible, feasible ccfDNA analysis. Methods: A prospective cohort of 125 patients with chronic liver disease was analyzed. Patients with incomplete clinical or laboratory data and patients without cirrhosis were excluded from the final analysis. Nonparametric tests, logistic regression and ROC curve analysis were performed. ccfDNA fragment size was measured using on-chip electrophoresis. Results: ccfDNA fragment size was significantly lower in the cirrhosis-HCC subgroup compared to the cirrhosis-only subgroup (p < 0.001). While AFP remains an independent predictor of HCC among cirrhosis patients, ccfDNA fragment size did not prove to be an independent predictor in this cohort. AUROC (area under the receiver operating characteristic curve) analysis revealed that a combined model of AFP, age, liver reserve, and ccfDNA fragment size did not perform better than the corresponding panel without ccfDNA. Moreover, after DeLong comparison, the difference between the two AUROCs proved statistically insignificant. Age and platelet count remain the strongest independent predictors in our exploratory cohort. Conclusions: Although ccfDNA fragment size proved to be lower in the HCC subgroup, its statistical significance fades when included into a multimarker panel. However, all panels should undergo further validation in a larger cohort, in order to better assess the individual contribution of each parameter and to discriminate between added diagnostic value and confounding effect of age and liver reserve parameters. Full article

Acute myeloid leukemia (AML) is one of the most common types of hematological malignancies and a leading cause of cancer deaths. It is characterized by the rapid accumulation of typically immature myeloid cells that serve to disrupt the production of mature cells, leading to a range of clinical sequelae. The role of recurrent chromosomal aberrations has long been appreciated in this disease, but a myriad of gene mutations have been increasingly acknowledged as having important roles. This review provides a comprehensive overview of the mutational landscape of AML, discussing the various genetic lesions in terms of their function, classification, etiological role, prognostic value, therapeutic impact, detection, and monitoring, with a particular focus on gene mutations. Full article