While strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibody‒drug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared with chemotherapeutic drugs, ADCs have the advantages of good tolerance, accurate target recognition, and small effects on noncancerous cells. ADCs occupy an increasingly important position in the therapeutic field. Currently, there are 13 Food and Drug Administration (FDA)‒approved ADCs and more than 100 ADC drugs at different stages of clinical trials. This review briefly describes the efficacy and safety of FDA-approved ADCs, and discusses the related problems and challenges to provide a reference for clinical work.

Background: Metastasis-associated protein 2 (MTA2) is a member of the metastasis-associated transcriptional regulator family and is a core component of the nucleosome remodeling and histone deacetylation complex. Despite growing evidence that MTA2 plays a crucial role in the tumorigenesis of certain cancers, no systematic pan-cancer analysis of MTA2 is available to date. Therefore, the aim of our study is to explore the prognostic value of MTA2 in 33 cancer types and to investigate its potential immune function. Methods: by comprehensive use of databases from TCGA, GTEx, GEO, UCSC xena, cBioPortal, comPPI, GeneMANIA, TCIA, MSigDB, and PDB, we applied various bioinformatics approaches to investigate the potential role of MTA2, including analyzing the association of MTA2 with MSI, prognosis, gene mutation, and immune cell infiltration in different tumors. We constructed a nomogram in TCGA-LIHC, performed single-cell sequencing (scRNA-seq) analysis of MTA2 in hepatocellular carcinoma (HCC), and screened drugs for the treatment of HCC. Finally, immunohistochemical experiments were performed to verify the expression and prognostic value of MTA2 in HCC. In vitro experiments were employed to observe the growth inhibition effects of MK-886 on the HCC cell line HepG2. Results: The results suggested that MTA2 was highly expressed in most cancers, and MTA2 expression was associated with the prognosis of different cancers. In addition, MTA2 expression was associated with Tumor Mutation Burden (TMB) in 12 cancer types and MSI in 8 cancer types. Immunoassays indicated that MTA2 positively correlated with activated memory CD4 T cells and M0 macrophage infiltration levels in HCC. ScRNA-seq analysis based on the GEO dataset discovered that MTA2 was significantly expressed in T cells in HCC. Finally, the eXtreme Sum (Xsum) algorithm was used to screen the antitumor drug MK-886, and the molecular docking technique was utilized to reveal the binding capacity between MK-886 and the MTA2 protein. The results demonstrated excellent binding sites between them, which bind to each other through Π-alkyl and alkyl interaction forces. An immunohistochemistry experiment showed that MTA2 protein was highly expressed in HCC, and high MTA2 expression was associated with poor survival in HCC patients. MK-886 significantly inhibited the proliferation and induced cell death of HepG2 cells in a dose-dependent manner. Conclusions: Our study demonstrated that MTA2 plays crucial roles in tumor progression and tumor immunity, and it could be used as a prognostic marker for various malignancies. MK-886 might be a powerful drug for HCC.

Mendelian randomization (MR) was employed to investigate the causal relationships between immune cell phenotypes, hyperthyroidism (HD), and potential metabolic mediators. In this study, we acquired 731 immune cell phenotypes from genome-wide association studies (GWAS) (n = 18,622), HD data from the research by Handan Melike Dönertaş et al. (3,731 cases, 480,867 controls), and aggregated statistics of 1,400 blood metabolites from UK Biobank (n = 115,078). Bidirectional MR analysis was performed to explore the causal relationships between the immune cell phenotypes and HD, and two-sample and multi-variable MR were conducted to identify the potential plasma metabolites mediating in HD. In addition, sensitivity analyses were used to evaluate robustness, heterogeneity, and horizontal pleiotropy of results. Single-cell transcriptome-based exploration of potential key molecule and mechanism by which plasma metabolites regulated the immune cell differentiation in HD pathogenesis. Co-localization analysis was using single-cell eQTL (sc-eQTL) data with key molecule to probe genetically shared effects. Two-sample MRshowed that CD25 on naive-mature B cell, CD8 + NKT cell, and thymol sulfate level were found to have causal relationships with HD (P < 0.008). The causal relationship between thymol sulfate and HD were further validated in an independent cohort using the inverse-variance weighted (IVW). In addition, CD25 on naive-mature B cells and CD8 + NKT cells were both negatively correlated with thymol sulfate (P < 0.05). The results remained significant after MR-Egger and MR-PRESSO correction for horizontal pleiotropy and heterogeneity (P > 0.05). Multi-variable MR results showed that CD25 on naive-mature B cell and CD8 + NKT cell mediated 8.67% and 10.4% of the associations between thymol sulfate and HD, respectively. Moreover, thymol sulfate mediated the evolution of CD8 + NKT cells in the immune microenvironment, identifying PTPRC, PTK2B, KDM5A and TIGIT as the key participating molecules. Co-localization analysis showed that the key molecules had significant genetic sharing effects with CD8 + NKT cells (PPH4 > 0.75, R2 > 0.8, P < 0.05), with PTK2B having the broadest sharing interval. Current MR study provides evidence supporting causal relationships between several specific immune cell phenotypes and HD, as well as potential mediating metabolites. Thymol sulfate may increases the risk of HD pathogenesis by mediating the evolution of PTK2B genetic variants inducing CD8 + NKT cells in the progression of the immune microenvironment.

Background: Hashimoto’s thyroiditis (HT) is the most common comorbidity in patients with papillary thyroid microcarcinoma (PTMC). The necessity of prophylactic central lymph node dissection (CLND) in clinically node-negative (cN0) PTMC cases remains a topic of debate. This study evaluates the risk of cervical lymph node metastasis (LNM) in PTMC patients with concurrent HT. Objectives: This study aims to evaluate the risk of central lymph node metastasis (CLNM) in patients with PTMC concurrent with HT. By synthesizing existing literature and conducting a case–control analysis, we seek to enhance individualized risk assessment and inform surgical decision-making for PTMC patients. Methods: We conducted a search for studies published before 1 June 2025 that assessed the risk of CLNM in PTMC concurrent with HT on PubMed, Embase, and Web of Science. A total of 17 studies involving 11,873 cases were included in this meta-analysis. Additionally, we performed a case–control study through a retrospective analysis of 303 consecutive PTMC patients who underwent surgery between 2017 and 2024. Results: The meta-analysis indicated that HT was present in 3,175 of the 11,873 PTMC cases (26.7%). The rate of positive CLNM was significantly lower in the HT group (32.6%) compared to the non-HT group (38.4%), with an odds ratio of 0.75. The false-negative rate was as low as 27.5% when combining ultrasonography (US) and fine-needle aspiration biopsy (FNAB) to evaluate CLN status. Funnel plots showed no significant publication bias. In the retrospective analysis, the CLN examination rate in the HT group was significantly higher than in the non-HT group, yet the incidence of CLNM was lower in the HT group. ROC curve analysis indicated that the TPOAb cutoff point for CLNM was 17.9, with sensitivity and specificity values of 53% and 68%, respectively. Conclusion: HT may reduce the risk of CLNM in patients with PTMC, suggesting a protective role. Predictive, preventive, and reliable preoperative evaluations using ultrasound and FNAB enhance the assessment of lymph node status, with TPOAb serving as an important marker. These insights support the development of personalized strategies for early intervention and improved patient management in PTMC. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251174681.