Adding cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy (ET) is considered the first-line treatment of advanced HR-positive/HER2-negative breast cancer. However, with the recent approval of several additional targeted agents, the optimal treatment sequencing remains uncertain, and it is unclear whether the benefits of CDK4/6i extend beyond progression on first-line therapy.

Brain metastases (BMs) are the most common intracranial malignancy, often arising from lung, breast, and melanoma cancers. Receptor tyrosine kinases, such as EGFR and HER2, drive tumor progression and resistance to therapy. Noninvasive detection of these biomarkers, especially in brain metastases, is crucial due to challenges with traditional biopsy methods. This systematic review and meta-analysis assess machine learning (ML)-based models for detecting EGFR mutations and HER2 overexpression in metastatic brain adenocarcinoma using MRI-derived radiomic features.

Over the years, accumulating evidence has been associating interleukin-13 gene (IL-13) variants with a wide array of chronic inflammatory diseases. Also, recent findings have associated the potential role of a single nucleotide polymorphism (SNP) of IL-13, rs20541, to promote either anti- or pro-inflammatory responses in chronic inflammatory diseases. Although rs20541 has been widely associated with various immune-related and inflammatory conditions, its precise functional relevance in the pathogenesis of human diseases has yet to be fully clarified. Nonetheless, its consistent associations and known effects on IL-13 signalling underscore its potential biological importance. Hence, this meta-analysis aimed to investigate the associations between IL-13 SNP rs20541 with distinct groups of chronic inflammatory diseases. Eligible studies were selected from seven databases including PubMed, EBSCO Host (all databases), Medline, CINAHL Plus, Scopus, SNPedia and GWAS. In total, 45 case-control studies with 16,045 cases and 23,312 controls were categorised into four major groups: atopic, cardiopulmonary and autoimmune diseases as well as cancer and tumour. While no consistent associations emerged for asthma or overall atopic and cardiopulmonary groups, protective associations for psoriasis and glioma were observed across multiple genetic contrasts. The A allele of rs20541 was significantly associated with higher risk of chronic obstructive pulmonary diseases (COPDs) [1.17 (1.03-1.32)] but reduced risk of cardiovascular diseases (CVDs) [0.87 (0.75-1.00)], psoriasis [allele model: 0.71 (0.65-0.77); dominant model: 0.69 (0.62-0.76)], overall cancer [allele model: 0.82 (0.66-0.98); dominant model: 0.82 (0.67-0.98) and glioma [allele model: 0.82 (0.68-0.95); dominant model: 0.72 (0.57-0.87)]. In subgroup analysis and meta-regression, sources of between-study heterogeneity were associated with ethnicity, age, gender and sample size in respective disease groups (pz < 0.05, pres > 0.05). Overall, this meta-analysis demonstrates that IL-13 rs20541 is a key immunogenetic variant exerting context-dependent effects, either via direct lgE-dependent or indirect regulatory effects across chronic inflammatory diseases. These mechanistic differences help explain why rs20541 confers susceptibility in some diseases while providing protection in others, reflecting the pleiotropic and tissue-specific functions of IL-13. Future research should integrate transcriptional studies and eQTL analyses of rs20541 to clarify its downstream impact on inflammation-specific genes, ultimately informing cytokine-targeted therapies to more precisely manage and prevent chronic inflammatory disease.

This study aims to conduct a systematic review of the prognostic value of miR-21 expression levels in patients with colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and esophageal squamous cell carcinoma (ESCC).

ALK receptor tyrosine kinase (ALK) rearrangements occur in 4-8% of non-small cell lung cancer (NSCLC) and are often associated with aggressive clinical behavior. Although ALK-targeted tyrosine kinase inhibitors significantly improve overall survival in advanced-stage NSCLC, their role in early-stage disease remains unclear. This meta-analysis (PROSPERO CRD420251012874) aimed to systematically evaluate recurrence rates and disease-free survival (DFS) outcomes in surgically resected patients with ALK-rearranged NSCLC compared to ALK-wild type (WT).

To date, no meta-analysis has studied the general outcomes of personalized cancer drug therapy with a focus on current targeted, immunotherapy, and multi-agent phase II clinical trials.

Head and neck adenoid cystic carcinoma (ACC) is a common malignancy often associated with an aggressive clinical course and a wide array of gene mutations. This systematic review aimed to determine the prevalence of these mutations and their association with prognosis and recurrence in ACC. A search of the scientific literature was carried out from inception till 31 July 2024 in the electronic databases - PubMed, EMBASE, Scopus, Web of Science, Ovid/MEDLINE, and Science direct following specific eligibility criteria. The methodological quality of the included studies was assessed using the Newcastle-Ottawa tool. 31 studies were included, and numerous genes like MYB, NOTCH, TP53, PIK3CA, ARID1A, KDM6A, RAS, SPEN, and many more were identified and were related to poor prognosis. Identification of different genes using wide NGS panels and combination of molecular techniques becomes necessary as multiple genes might be involved in ACC pathogenesis and subsequent targeted therapies can be designed.

Immune checkpoint inhibitors (ICIs) are used in epidermal growth factor receptor (EGFR)-mutant nonsmall-cell lung cancer (NSCLC) after resistance to targeted therapy; however, responses remain limited. This study identified predictors of ICI efficacy to inform treatment strategies.

P53 mutation (TP53m) is a common intrinsic factor involved in relapsed or refractory (R/R) B cell malignancies that associates with treatment resistance. As a novel immunotherapy, CAR-T has been increasingly applied in TP53m B cell malignancies, yet whether it can overcome the poor outcome of the TP53m population is controversial. We searched MEDLINE and EMBASE to identify population-based cohort studies that evaluated the CAR-T treatment outcomes between wild type and TP53m patients in B cell malignancies. Meta-analysis on their complete response (CR), partial response (PR), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) was carried out and pooled risk ratios (RR) or hazard ratios (HR) were estimated. A total of 10 eligible studies reporting 848 patients with B cell malignancies from wild type and TP53m groups receiving CAR-T therapy were selected. The CR and ORR were comparable in both wild type and TP53m patients either with B cell lymphoma or leukaemia (all p > 0.05). However, the TP53m group was associated with shorter PFS and OS in both diseases (all p < 0.05). In traditional single targeting CAR-T therapy, the PFS and OS were shorter in the TP53m group than in the wild type group (all p < 0.05). In contrast, the former outcomes of the wild type and TP53m groups were comparable when receiving dual-targeting CAR-T treatment (all p > 0.05). Though the CR and ORR of wild type and TP53m groups were similar, the PFS and OS of B cell malignancy patients bearing TP53m were inferior to wild type patients receiving CAR-T cell treatment. Notably, the CR, PFS and OS of wild type and TP53m groups exhibit the same therapeutic effect via CD19/22 CAR-T cocktail therapy. In other words, the poor prognosis of TP53m patients may be overcome by double targeting CAR-T mode.

Fms-like tyrosine kinase 3 (FLT3) mutations are associated with poor prognosis in patients with acute myeloid leukaemia (AML).

BRAF V600E-mutated metastatic colorectal cancer (mCRC) represents a biologically aggressive subset with poor prognosis and limited response to conventional therapies. While dual inhibition of BRAF and EGFR with encorafenib and cetuximab has emerged as a promising therapeutic strategy, a comprehensive quantitative synthesis of its efficacy and safety has been lacking.

Although cadmium (Cd) exposure has been implicated in lung cancer development, systematic investigations into its association with cancer mortality, particularly lung cancer mortality remain limited, and the molecular mechanisms driving Cd-induced tumor progression are not fully understood. In this study, we first conducted a meta-analysis of existing cohort studies to quantitatively assess the association between Cd exposure and cancer- and lung cancer-specific mortality. We then employed an integrative approach combining bioinformatics analyses, LASSO regression, and Mendelian randomization to identify and validate DHX34 as a key gene implicated in Cd-related lung carcinogenesis. These findings were further supported by molecular docking, molecular dynamics simulations, in vitro functional assays, and in vivo tumor models. Our meta-analysis showed that long-term Cd exposure significantly increased cancer mortality risk, especially in males (RR = 1.49, 95 % CI: 1.13-1.96) and in lung cancer (RR = 1.86, 95 % CI: 1.36-2.54). Integration of GSE165549 and TCGA data identified 36 Cd-related genes enriched in tumor associated pathways including cell cycle and DNA replication. LASSO regression and Mendelian randomization suggested a causal role of DHX34 in lung cancer. Molecular docking demonstrated a strong binding affinity between Cd2 + and DHX34 (binding free energy = -5.34 kcal/mol), and molecular dynamics simulations confirmed the stability of this complex. Functional assays further showed that CdCl2 exposure upregulated DHX34, thereby promoting lung cancer cell proliferation and tumor growth both in vitro and in vivo. Together, these findings provide multi-level evidence that DHX34 mediates Cd-induced lung cancer progression, highlighting the carcinogenic potential of environmental heavy metal exposure and offering new insights into molecular targets for early prevention, risk stratification, and therapeutic intervention.

The X-ray repair cross-complementary group 1 (XRCC1) gene 399 codon polymorphism may alter the structure of DNA repair enzymes to regulate DNA repair capacity. Impaired DNA repair ability can lead to the development of cancers such as prostate cancer (PCa). Although the association between the XRCC1 codon 399 polymorphism and the risk of PCa has been widely reported, the results have not been clear. Data were collected from PubMed, EMBASE, the Wanfang Database, CNKI and the Web of Science. A total of 20 case‒control studies were selected for inclusion in this updated analysis to determine the association between the XRCC1 codon 399 polymorphism and the risk of PCa. The crude odds ratio (OR) and 95% confidence interval (CI) were calculated using Stata (version 18) software to evaluate the association between the XRCC1-Arg399Gln polymorphism and prostate cancer. We identified 20 eligible reports that included 5803 cases of prostate cancer and 5470 controls. Our meta-analysis revealed a significant association between the XRCC1-Arg399Gln polymorphism and the risk of prostate cancer. In particular, according to the recessive models, this polymorphism was associated with a significantly increased prevalence of prostate cancer in Asian populations (AA versus AG + GG: OR = 1.255, 95% CI = 1.063-1.481, P = 0.507, I2, < 25%). Based on these results, the XRCC1-Arg399Gln polymorphism may be a risk factor for prostate cancer and can be used as a biomarker to predict the prognosis of prostate cancer.

Pancreatic cancer (PC) is a highly aggressive malignancy known for its late diagnosis and poor prognosis, making it one of the leading causes of cancer-related mortality worldwide. Identifying the molecular alterations involved in the prognosis of PC is essential. One such factor is HER3 overexpression, which can contribute to cancer cell survival, metastasis, and reduced overall survival (OS) in patients by activating cellular signaling pathways. This meta-analysis investigates the rate of HER3 overexpression in pancreatic cancer patients and examines how this overexpression affects their survival rates.

Overexpression of p16 has been documented in a variety of human tumours. Nonetheless, the association between p16 overexpression and the clinicopathological characteristics of patients with cervical cancer remains a subject of debate. This meta-analysis sought to systematically assess the relationship between p16 expression and the clinicopathological features of patients with cervical cancer.

Patients with BRCA1/2 pathogenic gene variants (PGVs) have an increased risk for breast, ovarian, pancreatic, and prostate cancer, with emerging evidence suggesting an association with melanoma. We aim to evaluate the strength of the melanoma association to guide cancer risk-management recommendations.

This meta-analysis aims to assess the diagnostic performance of artificial intelligence (AI) based on magnetic resonance imaging (MRI) in detecting molecular subtypes of pediatric medulloblastoma (MB) in children.

Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine carcinoma (NEC) with poor prognosis due to chemotherapy resistance. Molecular subtypes, including ASCL1, NEUROD1, YAP1 and POU2F3, have distinct clinical implications. POU2F3, linked to a tuft cell-like lineage, represents a non-neuroendocrine subtype found in SCLC and extrapulmonary NECs. However, its prognostic and clinical significance remain unclear.

To evaluate the efficacy and explore the potential mechanism of curcumin for the treatment and prevention of NSCLC. We searched six databases thoroughly for articles published before December 2024. Stata 15.0 software was applied for systematic review with meta-analysis. We utilized network pharmacology, Mendelian randomization, and molecular docking techniques to investigate the pharmacological properties and potential targets of curcumin in the treatment of NSCLC. Twenty-four studies involving 392 experimental animals were included in this study. Meta-analysis results showed that curcumin significantly reduced tumor volume of mice (p < 0.001) in the NSCLC group compared to the control group. Two hundred twenty-nine curcumin target genes were predicted. 1546 NSCLC-related genes were obtained by taking the intersection of DEGs and genes in the key module of WGCNA. Eight hub genes were identified by protein-protein interaction. The eight hub genes showed significant clinical value and were found to be negatively correlated with the majority of immune cell infiltration. Molecular docking results indicated a good binding affinity between these eight hub genes and curcumin. Mendelian randomization demonstrated a causal relationship between the AURKB level and the increased risk of NSCLC. In this study, the effectiveness of curcumin has been demonstrated in in vivo models of NSCLC by meta-analysis. AURKB has been identified as a high-risk target for NSCLC by network pharmacological analysis and MR for the first time. Our study provides a scientific basis for clinical applications of curcumin in NSCLC.

The causal relationship between immune cell signatures and multiple myeloma (MM) pathobiology remains incompletely understood. This study aimed to explore the bidirectional causal associations between 731 circulating immune cell traits and MM risk using a two-sample, bidirectional Mendelian randomization (MR) approach. Two-sample MR analyses were conducted utilizing genome-wide association study (GWAS) summary statistics for 731 immune cell phenotypes and MM GWAS datasets. Sensitivity analyses were performed to assess the robustness and reliability of the findings. Furthermore, meta-analyses were conducted on specific immune cell traits identified through the primary MR analyses to reinforce causal inferences. We identified 11 immune cell traits across 3 immune profiles - absolute cell count (AC), relative cell (RC) frequency, and median fluorescence intensity (MFI) - that exhibited significant causal associations with MM. Three immune traits were associated with an increased risk of MM: CD39+ CD8br %CD8br (P < .001), CD20 on CD20- CD38- cells (P = .002), and CD38 on transitional cells (P < .001). Conversely, 8 immune traits were found to confer a protective effect against MM, including CD11c+ monocyte AC (P = .002), Im myeloid-derived suppressor cell (MDSC) %CD33dim HLA-DR- CD66b- (P = .002), CD8dim %T cell (P < .001), CD8dim %leukocyte (P < .001), CD24 on CD24+ CD27+ cells (P = .003), CD4 on naive CD4+ cells (P < .001), CD11b on Mo MDSCs (P = .002), and HLA-DR on CD33dim HLA-DR+ CD11b- cells (P < .001). The reverse MR analysis demonstrated a significant causal association between the expression of CD19 on CD24+ CD27+ B cells and CD16 on CD14+ CD16+ monocytes in MM. These findings were validated through sensitivity tests and meta-analyses, which confirmed the robustness of the results and the absence of significant heterogeneity. Our bidirectional MR analyses provide compelling evidence for causal relationships between specific immune cell phenotypes and MM risk. These insights deepen the understanding of immune system dysregulation in MM pathogenesis and highlight potential immune-related targets for future therapeutic interventions.