The prognostic value of SMAD4 in pancreatic cancer has been evaluated in several studies. However, the conclusions remain controversial. Therefore, we aimed to evaluate the prognostic value of the SMAD4 gene in pancreatic cancer to aid in the design of therapeutic strategies.

The efficacy of CD38 monoclonal antibody (mAb)-based quadruplet regimens versus triplet regimens in newly diagnosed multiple myeloma (NDMM) patients with high-risk cytogenetics remains controversial. This meta-analysis aims to consolidate evidence from randomized controlled trials (RCTs) to resolve this clinical uncertainty.

Previous evidence suggests that higher prepubertal adiposity protects against breast cancer risk. Whether this protection extends into early adulthood remains uncertain. We conducted genome-wide association studies on body mass index (BMI) in nulliparous women from menarche to <40 years across five cohorts, with additional analyses in three subintervals of this life stage. Results were meta-analyzed, and two-sample univariable and multivariable Mendelian randomization was applied within a lifecourse framework to assess the effect of BMI on breast cancer risk. Between menarche and <40 years, we observed heterogeneity in genetic effects. Genome-wide correlations further suggest that BMI during this early adult period may be partly influenced by distinct genetic factors compared with adiposity at other life stages. Higher genetically proxied BMI between menarche and 40 years reduced breast cancer risk. This protective effect attenuated after adjusting for prepubertal adiposity. These findings refine our understanding of adiposity's role in breast cancer and highlight earlier life stages as critical windows for risk modulation.

Background/Objectives: Stemness has been proposed as a unifying driver of invasion, treatment resistance, and relapse in oral squamous cell carcinoma (OSCC). We synthesized two complementary evidence streams to determine whether higher stemness predicts poorer survival in OSCC: (i) computational stemness signatures derived from transcriptomic/epigenetic data and (ii) tissue cancer stem cell (CSC) immunophenotypes by immunohistochemistry (IHC). Methods: Following PRISMA 2020, we searched PubMed/MEDLINE, Embase, Scopus, and SciELO. Adults with histologically confirmed OSCC were eligible. Primary outcome was overall survival (OS); disease-specific survival (DSS) and recurrence-free survival (RFS) were secondary. Two parallel meta-analyses pooled effects within domains; random-effects restricted maximum likelihood (REML) models were applied. Results: Of 785 records, 11 studies met criteria. For computational signatures (k = 6), higher stemness was associated with poorer OS (pooled HR 2.24, 95% CI 1.61-3.12; I2 ≈ 49%). Sensitivity excluding the single unadjusted Kaplan-Meier (KM)-derived estimate yielded a similar effect (HR 2.13, 95% CI 1.56-2.89). For CSC-IHC (main analysis, k = 2), CSC-positive profiles predicted worse OS (pooled HR 2.01, 95% CI 1.42-2.84; I2 ≈ 0%); results were robust to excluding an internally inconsistent study (single-study HR 2.078). An exploratory sensitivity analysis, including a 1-year HR (different time horizon), increased heterogeneity and was not considered definitive. A functional meta-synthesis converged on epithelial-mesenchymal transition/extracellular matrix remodeling, hypoxia/glycolysis, redox/ferroptosis resistance, and ribosome/rRNA biogenesis, supporting biological plausibility across modalities. Conclusions: Across computational and IHC evidence, stemness consistently portends inferior OS in OSCC, offering a biologically anchored framework for risk stratification and testable therapeutic hypotheses.

To investigate the association and shared pathogenic mechanisms between systemic lupus erythematosus (SLE) and thyroid cancer (TC) using an integrative multi-omics framework.

KRAS is a common driver gene in non-small cell lung cancer (NSCLC). Owing to the absence of universally effective targeted agents and marked heterogeneity, optimal treatment selection for KRAS-mutant NSCLC remains uncertain. This study combined network meta-analysis (NMA) with real-world evidence to inform precision treatment strategies.

Endocrine therapy (ET) plus CDK4/6 inhibitors (CDK4/6i) remains first-line (1 L) standard for ER+/HER2- metastatic breast cancer (mBC). However, ESR1 mutations lead to ET resistance and subsequent disease progression (PD). Limitations of intramuscular fulvestrant have led to the development of novel oral selective estrogen receptor degraders (SERDs). We aim to evaluate efficacy and safety of novel oral SERDs for ER+/HER2- mBC.

The optimal first-line treatment for Rat Sarcorma Virus (RAS) wild-type metastatic colorectal cancer remains undetermined. Several studies have compared the efficacy of different first-line regimens, including doublet- or triplet-chemotherapy (CT) alone or in combination with targeted therapies (anti-EGFR/anti-VEGF), without conclusive results.

Early-onset gastric cancer (EOGC), diagnosed before age 50, is characterized by distinct clinicopathological features, though its molecular landscape remains poorly defined.

Glioblastoma (GBM) inevitably recurs despite maximal safe resection and standard chemoradiotherapy. The factors influencing survival after first recurrence and re-resection remain controversial.

This meta-analysis aimed to evaluate the association between distinct KRAS mutations and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) patients.

Dioxins, are highly potent environmental carcinogens. Their toxic effects are mediated primarily by the Aryl Hydrocarbon Receptor (AhR). A comprehensive understanding of how AhR-induced genetic and epigenetic alterations drive carcinogenesis, especially through effects on cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT) and transgenerational inheritance, remains imperative.

Despite the availability of several validated therapies, the optimal second-line regimen for EGFR-mutant non-small cell lung cancer (NSCLC) after tyrosine kinase inhibitor (TKI) failure remains uncertain.

The primary objective of this study is to evaluate the efficacy of various pharmaceuticals (combination therapy versus monotherapy) in patients with glioblastoma (GB) with abnormal epidermal growth factor receptor (EGFR) genes. Clinical trials to investigate the therapeutic effects of different therapy was searched by PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar. The Cochrane Risk of Bias Assessment Tool and data analysis software will be applied. Data collection spanned from the earliest available date up to April 2025. Eight studies involving a total of 2,137 individuals were included, with 657 of these receiving combination therapies and 1,480 receiving monotherapies. The analysis revealed that combination therapies generally demonstrated superior efficacy compared to the single ones, while monotherapies exhibited greater potency than temozolomide (TMZ). In terms of median progression-free survival (PFS), the combinations of Afatinib plus TMZ (SUCRA: 62.28%), rindopepimut (CDX-110) plus TMZ (SUCRA: 62.27%), and depatuxizumab mafodotin (Depatux M) plus TMZ (SUCRA: 54.4%) ranked among the top tier. For median overall survival (OS), the combinations of CDX-110 plus TMZ (SUCRA: 68.8%), Depatux M plus TMZ (SUCRA: 68.3%), and Nimotuzumab plus TMZ (SUCRA: 52.5%) were positioned in the upper echelon. In terms of prolonging both median PFS and median OS in GB, CDX-110 plus TMZ and Depatux M plus TMZ have shown slightly better than comparable therapies. However, further clinical trials are needed to confirm the effectiveness of other drugs in this respect.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology has recently been discovered for gene editing and cancer therapy and its applications are expanding. This review and meta-analysis aim to assess the present and future of CRISPR/Cas9 based gene editing in cancer treatment and the way forward.

Proteins have an integral role in cancer aetiology and inform cancer detection, treatment, and prognosis. While published data from prospective proteomic studies identifying early detection cancer risk markers have rapidly increased in the past five years, the landscape of evidence remains unclear. We aim to synthesise the evidence on circulating proteins and cancer risk.

Oral squamous cell carcinoma remains a significant global health burden, largely due to delayed diagnosis and limited prognostic tools. MicroRNAs (miRNAs), as post-transcriptional gene regulators, have shown promise as biomarkers for both early detection and outcome prediction. However, variability in study design, analytical approaches, and biospecimen sources has hindered clinical translation. This meta-analysis aimed to synthesize current evidence on the diagnostic accuracy, prognostic significance, and differential expression of miRNAs in oral cancer.

Risk-reducing bilateral mastectomy reduces the incidence of breast cancer in female carriers of the BRCA pathogenic variants, but its association with mortality remains uncertain.

Lymphomas are biologically heterogeneous malignancies with multifactorial etiologies involving genetic, environmental, and immune dysregulation. The functional variant rs1049174 SNP in the KLRK1 gene (encoding NKG2D) regulates NKG2D expression and modulates NK cells immune surveillance pathways, which may influence lymphoma susceptibility. We investigated this association through a two-stage case-control study and meta-analysis. First, we analyzed 246 diffuse large B-cell lymphoma (DLBCL) patients and 599 healthy controls (exploratory cohort), followed by a confirmatory cohort of 234 non-Hodgkin lymphoma (NHL)/Hodgkin lymphoma (HL) patients. Genotype frequencies were assessed via chi-square tests, with odds ratios (ORs) calculated for risk associations. A systematic review and meta-analysis of 10 studies, including our cohorts (3,785 cases and 4,129 controls), testing rs1049174 and cancer risk was also conducted. In the exploratory cohort, the GG genotype showed no significant association with overall lymphoma risk (OR = 0.83; 95% CI: 0.61-1.13; *p* = 0.25). However, in NHL, the GG genotype was underrepresented (OR = 0.75; 95% CI: 0.57-0.99; *p* = 0.02). Pooled lymphoma analysis revealed a protective effect (OR = 0.78; 95% CI: 0.62-0.99; *p* = 0.03). Meta-analysis confirmed a significant protective role of the GG genotype against cancer (OR = 0.71; 95% CI: 0.63-0.79), despite heterogeneity and potential publication bias. Our findings suggest that the rs1049174 GG genotype is associated with reduced lymphoma susceptibility, particularly in NHL, underscoring the importance of immunogenetic variants in lymphomagenesis. Further functional and clinical studies are needed to elucidate the mechanistic basis of this association.

Leukemias are heterogenous hematologic malignancies broadly classified into myeloid and lymphoid lineages, each with distinct molecular and clinical features. Here we aime to identify lineage-specific molecular vulnerabilities in myeloid and lymphoid leukemias and use them to guide targeted therapy and rational drug repurposing.