The impact of BRAF p.V600E mutation on the pathogenesis of mixed odontogenic tumors remains uncertain. We conducted a systematic review and meta-analysis to determine the prevalence of BRAF mutation in mixed odontogenic tumors and to evaluate the correlation between this mutation and the clinical characteristics of these lesions. The study protocol was registered in PROSPERO (registration number CRD42025636575). A comprehensive search of the PubMed/MEDLINE, Embase, and Scopus databases was conducted. The study population included patients diagnosed with ameloblastic fibroma (AF), developing odontoma (DO), ameloblastic fibro-odontoma (AFO), ameloblastic fibro-dentinoma (AFD), odontoma (OD), odontogenic sarcoma (OS), or ameloblastic fibrosarcoma (AFS), with BRAF mutation detection results. The AFO, AFD, and DO were categorized in 1 group for further analysis. The study quality was assessed using the modified scale of the Agency for Healthcare Research and Quality for observational studies. A random-effects meta-analysis model was employed using Review Manager software. Statistical heterogeneity was assessed by forest plots, Tau-squared, Cochrane Chi-square, and I2 statistics. A total of 9 studies were included in the analysis. Overall, AFS demonstrated the highest BRAF mutation prevalence (71.4%), followed by AF (67.4%) and AFO/AFD/DO (55.6%), respectively. No OD cases exhibited this mutation. In addition, AF, AFO/AFD/DO, and AFS lesions exhibited significantly larger average sizes compared to OD. AFS demonstrated significantly higher recurrence rates than AFO/AFD/DO and OD. Additionally, a significant female predilection for BRAF-mutated AF was identified. BRAF mutation is associated with AF, AFO/AFD/DO, and AFS, but not OD. Its presence in a substantial portion of AFO/AFD/DO, together with their larger size compared to OD, could support a neoplastic nature in at least a subset of these lesions, though a hamartomatous DO may exist. Further investigation and clinical correlation remain essential to distinguish these entities.

PARP inhibitor (PARPi)-based therapy is a well-established treatment modality for metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) deficiencies. However, its clinical efficacy in mCRPC without HRR alterations remains undefined.

The DNA damage response (DDR) is a critical cellular mechanism for maintaining genomic stability and integrity. Over the past decade, targeting DDR pathways in tumors has led to significant therapeutic advances but faces limitations such as drug resistance and combinatorial toxicity. Meanwhile, cancer immunotherapy has shown remarkable efficacy in some solid tumors, yet response rates to single-agent therapies remain modest and are often hindered by immunosuppression in the tumor microenvironment (TME). DDR inhibitors (DDRi) can potentiate antitumor immunity via mechanisms such as increased neoantigen release and activation of the cGAS-STING pathway, providing a rationale for combining DDRi with immunotherapy. Indeed, the combination of DDRi with immune checkpoint inhibitors (ICIs) has shown synergistic promise in clinical studies, while combinations of DDRi with novel immunotherapeutic approaches are now in early development. Here, we systematically review DDR-targeted cancer therapies and their molecular mechanisms for enhancing tumor immunogenicity, along with recent clinical advances in combining DDRi with immunotherapy. Our goal is to provide a theoretical foundation and translational insight for optimizing these combination strategies.

DNA-based liquid biopsies, including circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA), are emerging as minimally invasive biomarkers for monitoring surgical and postsurgical outcomes in gynecologic malignancies. These tools offer the potential to guide early intervention, refine risk stratification, and improve prognostic accuracy. This systematic review aimed to assess the clinical utility of DNA-based liquid biopsies in evaluating recurrence, surgical success, and preoperative diagnosis in gynecologic cancers.

To compare the diagnostic test accuracy of Afirma GSC and ThyroSeq v3 in cytologically indeterminate thyroid nodules.

BACKGROUND: Therapy-related acute lymphoblastic leukemia (t-ALL) is an aggressive subtype of ALL that arises after cytotoxic therapy. It is associated with adverse cytogenetics and older age, but survival outcomes compared with de novo ALL remain uncertain. We aimed to systematically evaluate survival differences in adults with t-ALL versus d-ALL. METHODS: We performed a systematic review and meta-analysis according to PRISMA guidelines. PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library were searched to Dec 31, 2024. Eligible studies included adults (≥ 18 years) with t-ALL or de novo ALL reporting survival. Pediatric studies, case reports, reviews, and abstracts were excluded. Two reviewers independently screened and extracted data. Quality was assessed with the MASTER scale. Hazard ratios (HRs) for overall survival were pooled using Doi’s quality effects model. The protocol was registered with PROSPERO (CRD42025625294). RESULTS: From 3,325 records, 27 retrospective cohort studies (169,237 patients; 1,827 with t-ALL) were included. Nine studies (30,527 patients) were eligible for meta-analysis. The pooled HR for mortality in t-ALL versus d-ALL was 1.07 (95% CI 0.94–1.23), showing no significant survival difference. Median survival ranged from 6 to 32 months in t-ALL and 11–50.6 months in d-ALL. Poor-risk cytogenetics were more frequent in t-ALL (43–100% vs. 31–66%), with higher TP53 mutations (38% vs. 10%) and complex karyotypes. Complete remission was lower in t-ALL (60–88.9% vs. 81.5–93%). Heterogeneity was moderate (I²=50.5%) with evidence of small-study effects. CONCLUSION: Despite adverse biology, t-ALL demonstrates survival comparable to d-ALL with modern therapies, particularly allogeneic transplantation.

Matrix metalloproteinases (MMPs), especially MMP-2, MMP-7, and MMP-9, have key roles in breaking down of extracellular matrix components and participate in tumor invasion, metastasis, and poor prognosis in oral squamous cell carcinoma (OSCC). The main objective of this study was to systematically review and quantitatively synthesize available evidence on the expression of MMP-2, MMP-7, and MMP-9 in OSCC tissues, as well as their concentrations in serum and saliva, in order to assess their potential as diagnostic and prognostic biomarkers and to explore factors influencing their levels across different populations. The study followed PRISMA guidelines, and relevant English-language studies were identified with the help of a comprehensive search of six major databases. Studies were included with the data for MMP-2, MMP-7, or MMP-9 in OSCC tissues, serum, or saliva and had measurable outcomes. A total of 28 eligible studies were analyzed. The analyses showed significant expression of MMPs [0.085, CI 95 % (0.067-0107); I2 = 22.57; P = 0.000; Q = 45.20]. The analyses also showed significant concentration of MMPs [1.62, CI 95 % (0.90-2.33); I2 = 96.38; P = 0.000; Q = 46.81]. Meta-regression analysis showed that geographic region had a significant effect on MMP concentrations, with higher values for studies from Pakistan. However, other factors such as patient age, sampling location, and type of MMP were not statistically significant moderators. These findings support the potential of MMPs as prognostic biomarkers for OSCC. Differences between regions highlight the need for considering local factors in both clinical evaluation and future research design.

Autophagy and cellular senescence are fundamental determinants of tumor cell fate. p16INK4a has emerged as a key regulator at the intersection of these processes, yet its mechanistic role in the autophagy - senescence axis remains incompletely defined. Understanding this interaction is essential for identifying novel therapeutic opportunities in oncology. A systematic literature search was conducted across PubMed, Web of Science, and Scopus for studies published between January 2000 and April 2025, yielding 10 eligible studies after the application of predefined criteria. Evidence shows a dual role of autophagy in tumor biology. In some models, autophagy increased p16INK4a and senescence-associated β-gal activity, leading to stable growth arrest. Under stress conditions, however, it supported tumor cell survival despite senescence signals. Mechanistically, p16INK4a acted both upstream, modulating autophagic flux, and downstream, as an effector of autophagy-induced senescence. Study heterogeneity limited direct comparisons. Autophagy and p16INK4a interact bidirectionally to regulate senescence, representing a critical axis that can shift tumor cells between suppression and survival. Future research should prioritize standardized protocols, longitudinal models, and therapeutic evaluations to clarify whether targeting this pathway can be translated into effective cancer interventions.

Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in glutathione metabolism and oxidative stress regulation. Although it is traditionally viewed as a liver function marker, emerging evidence suggests that its aberrant expression is closely associated with tumorigenesis, progression, and therapeutic resistance across multiple solid tumors. However, the comprehensive landscape of the GGT gene family and its clinical value in tumor diagnosis and prognosis remain unclear.

To systematically evaluate preclinical evidence on the protective effects of herbal interventions against toxicant-induced genetic and epigenetic alterations in animal models.

Central nervous system (CNS) tumours occur when abnormal cells form in the tissues of the brain and/or spinal cord. Conventional testing for CNS tumour classification involves histopathological evaluation and molecular markers. More recently, DNA methylation-based classifier tests are being used as an adjunct tool in addition to conventional tests to help with CNS tumour classification. We conducted a health technology assessment of DNA methylation-based classifier tests for CNS tumours, which included an evaluation of effectiveness, cost-effectiveness, and budget impact of publicly funding DNA methylation-based classifier tests for CNS tumours. After considering the likely effects of testing on the patient experience, we determined not to perform an analysis of patient preferences and values.

Aberrant mucin expression is implicated in lower gastrointestinal tract (GIT) cancers, yet its clinicopathological relevance remains poorly understood. To identify distinct mucin signatures in association with (pre)tumour subtypes, anatomical location, and clinical outcomes, we conducted a systematic review and meta-analysis of MEDLINE articles published between January 2001 and September 2025. Studies were included if they assessed mucin expression in lower GIT (pre)malignant lesions. Fifty-eight studies were eligible. MUC2 and MUC5AC expression was upregulated in serrated polyps and mucinous- and microsatellite instability (MSI)-associated proximal adenocarcinomas, whereas a downregulation of MUC2 was noted in advanced adenomas and non-mucinous distal tumours. Discrepancies in survival in relation to high-level or low-level MUC2 further suggested that this glycoprotein cooperates with other mucins during carcinogenesis. Notably, abundant MUC1 expression was seen in adenomas with high-grade dysplasia and together with high-level MUC13 correlated with (non-)mucinous CRC types and poor prognosis. Similar mucin signatures were also found in small intestinal adenocarcinoma, yet MUC2 was downregulated and increased MUC5AC rather associated with a worse survival, emphasizing the role of tumour location in influencing tumour behaviour. In conclusion, aberrant mucin signatures reflect distinct molecular pathways in (pre)malignant GIT lesions and highlight their potential utility as biomarkers and therapeutic targets. Schematic representation of the main findings regarding altered mucin signalling in several precancerous lesions (adenomatous (i.e., conventional pathway 1) and serrated polyps (i.e. pathway 2)) and small intestinal (SIA) and colorectal (CRC) adenocarcinomas and its clinicopathological significance (outcome, anatomical location (proximal/distal), molecular subtypes (MSI, (non)-mucinous).

Solute Carrier Family 7 Member 11 (SLC7A11), a redox homeostasis and metabolism regulator, is frequently overexpressed and mutated in cancers, contributing to progression and therapy resistance. This study systematically reviewed and meta-analyzed its prognostic value, mutational landscape, role in resistance, and its therapeutic potential. A comprehensive search (2010-2024) across PubMed and ScienceDirect identified 236 studies, alongside TCGA data from 30 cancer types and 128 mutations from GDC. Prognostic and clinicopathological correlations were assessed using hazard ratios (HRs), with fixed/random effects models based on heterogeneity (I2), and significance tested via Z-tests (p < 0.05). Publication bias was evaluated using Begg's and Egger's tests. General linear models explored associations with resistance and pathway alterations. Interestingly, SLC7A11 overexpression was associated with poor prognosis (HR = 1.22), adverse clinicopathological features viz. TNM-stage and therapy resistance like chemoresistance (p < 0.001). Mutation analysis revealed diverse alterations and frequent heterozygous deletions, prevalently, missense mutation underscoring its oncogenic role. Moreover, SLC7A11 inhibitors, particularly sulfasalazine and erastin, effectively reversed resistance, in 18 clinical trials (Phase I-III) completed over the last decade. Targeting SLC7A11 presents a promising therapeutic strategy to modulate redox balance, metabolism, and ferroptosis, towards efficient cancer treatments.

Gliomas are among the most aggressive and diagnostically challenging brain tumors. Conventional pathways (MRI, histopathology, clinical assessment) have limited sensitivity for early or low-grade disease and introduce delays. Artificial intelligence (AI)-particularly deep learning (e.g., CNNs)-may enhance diagnostic precision and efficiency.

Circulating tumor DNA (ctDNA) profiling offers non-invasive insights for personalized prostate cancer management. This systematic review provides the first comprehensive appraisal of ctDNA assay methods, genomic targets, and their clinical correlations and proposes practical recommendations to guide future standardization and validation. We searched PubMed, ScienceDirect, Scopus, and the Cochrane Library starting December 2024 following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. From 229 records, 44 studies (10,631 patients) met the inclusion criteria. Plasma ctDNA analyzed by NGS predominantly profiled TP53 (72.7%), AR (70.4%), BRCA1/2 (61.3%), ATM (50%), RB1 (47.7%), and PTEN (41%). ctDNA positivity and specific key alterations correlated with poorer overall and progression-free survival. BRCA1/2-mutant patients benefited from Olaparib plus Abiraterone, while persistent alterations predicted early progression. Beyond synthesizing existing evidence, we identify key gaps, such as inconsistent reporting of variant allele fractions, limited diversity in study populations, and underexplored rare alterations. We recommend unified reporting standards (e.g., variant allele frequency thresholds and panel composition) and prioritized prospective trials to validate high-impact targets. These steps will accelerate the integration of ctDNA into routine precision oncology practice worldwide.

The signal transducer and activator of transcription 5 (STAT5) proteins, STAT5A and STAT5B, are highly homologous transcription factors with distinct roles in cancer biology. While STAT5A has been characterized as a context-dependent modulator of tumor progression, the prognostic significance of STAT5B remains less clear. Here, we conducted a systematic meta-analysis of STAT5B to evaluate its association with overall survival across cancers and to compare its prognostic role with that of STAT5A, as reported previously.

Genome-wide noninvasive prenatal testing has introduced new challenges in clinical interpretation, for example, due to discrepancies between noninvasive prenatal testing and confirmatory invasive results caused by confined placental mosaicism. These discordant cases often involve rare autosomal trisomies, frequently attributed to placental mosaicism. Complex, multichromosomal false-positive genome-wide noninvasive prenatal testing results are usually not due to placental mosaicism but rather to maternal malignancy, for example. This study aimed to assess chromosome-specific associations with pregnancy complications and uniparental disomy in false-positive rare autosomal trisomies and the prevalence of maternal malignancies in complex, multichromosomal genome-wide noninvasive prenatal testing results.

BRAF mutations are found in 10% of colon cancers (CCs) and are associated with poor prognosis in metastatic disease. BRAF V600E predicts sensitivity to cetuximab + encorafenib in the metastatic setting. With new trials testing encorafenib-containing regimens for early-stage CC, we sought to characterize the clinical outcomes of early-stage BRAF V600E CC.

BACKGROUND: The prognostic significance of NOTCH1 mutations in T-cell acute lymphoblastic leukemia (T-ALL) remains uncertain. This study evaluates their impact on key clinical outcomes. METHODS: A systematic search of the Cochrane Library, PubMed, and CINAHL identified eleven peer-reviewed studies encompassing 2,039 patients. Data were independently extracted by two reviewers and analyzed using RevMan 5.4.1. RESULTS: NOTCH1 mutations were associated with an approximately 22% improvement in event-free survival (EFS) across ten studies (pooled relative risk 0.63, 95% CI: 0.51–0.78), with corresponding EFS rates of 68.8% in NOTCH1-mutated cases versus 53.8% in wild-type cases. Although the improvement in prednisolone response (PR) across three studies was not statistically significant (pooled OR 1.41, 95% CI: 0.44–4.56; p = 0.56), complete remission (CR) rates in three studies were markedly higher in the NOTCH1-mutant group (pooled OR 8.53, 95% CI: 0.86–85.09). Overall survival (OS), evaluated in three studies, tended to be improved in patients with NOTCH1 mutations; however, substantial inter-study heterogeneity precluded definitive conclusions. CONCLUSIONS: These findings support incorporating NOTCH1 mutation status into clinical prognostication and treatment planning for T-ALL, potentially facilitating more personalized therapeutic strategies.

DNA promoter methylation is one of the main epigenetic mechanisms of silencing of tumor-suppressor genes in cancer. Accumulating scientific evidence has shown various genes with aberrant DNA methylation in oral cancer (OC), however, the magnitude of the association between DNA methylation and OC risk remains controversial.