Wenwen Zhang

Extracellular vesicles (EVs) play a crucial role as important mediators of intercellular communication in the progression of tumors. The capture and analysis of tumor-derived EVs offer new possibilities for the application of cancer liquid biopsies. This study aims to construct a DNA tetrahedral nanostructure that specifically recognizes HER2 and CD63, enabling the effective enrichment and detection of HER2-expressing EVs (HEVs). We enriched HEVs from cell lines and 13 random clinical samples and validated their characteristics by dynamic light scattering, transmission electron microscopy, and Western blotting. Further, we detected HEVs levels in clinical samples. The HEVs levels in HER2-positive breast cancer patients were significantly higher than those in healthy/benign controls (mean, 4.737 vs 4.160 vs 4.144 U/μL, P < 0.0001), displaying a concentration gradient across different HER2 expression levels. This study establishes an approach for HEV detection, thus providing a new tool for the diagnosis of HER2-positive breast cancer.

Non-coding RNAs in Breast Cancer -Volume II Non-coding RNAs (ncRNAs) represent a category of RNA that do not possess protein-coding capabilities, encompassing microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Despite their inability to encode proteins, ncRNAs play a crucial role in modulating the expression of various molecular targets, thereby influencing specific cellular biological processes and outcomes. To date, numerous ncRNAs have been identified and shown to be dysregulated across various cancer types, including breast cancer (1). Furthermore, the potential of ncRNAs as diagnostic and prognostic biomarkers, as well as therapeutic targets, has been thoroughly investigated in breast cancer (1,2). This research topic collected 12 articles (four original research studies, and eight reviews), which concentrated on novel discoveries or assessed recent advancements of ncRNAs in breast cancer.Firstly, a comprehensive review by Li et al. highlights the promise of two significant classes of non-coding RNAs, namely lncRNAs and miRNAs, as both diagnostic and prognostic biomarkers for breast cancer, as well as potential targets for innovative therapeutic approaches. Chen et al. conducted a comprehensive review on the substantial impact of lncRNAs on the progression, diagnosis, and effectiveness of neoadjuvant chemotherapy in triple-negative breast cancer (TNBC), highlighting the varied expression profiles of dysregulated lncRNAs. They provided a summary of the precise mechanisms through which lncRNAs modulate gene expression in both the nucleus and cytoplasm, influencing post-transcriptional processes that affect mRNA stability and translation efficiency, thereby regulating tumor cell growth, proliferation, and metastasis.ncRNAs have been reported to be involved in the regulation of signaling pathways for a variety of molecules or genes (3). 2-Methoxyestradiol (2ME2) is the primary endogenous metabolite of 17β-estradiol. It exhibits a diminished affinity for the estrogen receptor compared to 17β-estradiol and its derivatives, and its mechanism of action operates independently of the cellular response to estrogen (4). Subramani et al. found 2ME2 modifies the expression of pertinent genes by influencing the miRNome in TNBC cells, subsequently inhibiting TNBC through its impact on critical processes such as cell proliferation, apoptosis, and metastasis. Pyruvate kinase M2 (PKM2) serves as a crucial metabolic enzyme within the glycolytic pathway (5) Investigating SNPs elucidates the variations in individual predisposition to diseases, disparities in pharmacological responses, and differences in reactions to environmental stimuli (8). The findings of Qi et al. confirmed that specific LncRNA H19 gene polymorphisms are linked to an increased susceptibility to breast cancer, and that the expression levels of associated genetic markers can profoundly influence the prognosis and therapeutic response in patients with breast cancer. circRNAs are extensively investigated for their role as molecular sponges for miRNAs, which compete for binding to miRNA-targeted messenger RNAs (9). This interaction contributes to the establishment of a sophisticated post-transcriptional regulatory framework known as the competitive endogenous RNA (ceRNA) network (9). In this research topic, Liu et al. found EIF4A3 could enhance the expression of circ_0022382, and elevated levels of circ_0022382 may activate the PI3K/AKT/mTOR signaling pathway and SLC7A11 by sequestering let-7a-5p. Conversely, the silencing of circ_0022382 can impede the proliferation and migration of breast cancer cells, while also promoting the onset of disulfidptosis in breast cancer.Exosomes represent a category of extracellular vesicles encased in a lipid bilayer, lacking intracellular organelles yet encompassing all known molecular components found within a cell. Tumor cells release exosomes approximately ten times greater than that of normal cells (10). These tumor-derived exosomes play a crucial role in mediating intercellular communication and are implicated in various phases of cancer progression (10). Primary breast tumor cells have been shown to sensitize brain microenvironmental cells, facilitating the development of breast cancer brain metastasis (BCBM) via the secretion of extracellular vesicle-associated miRNAs (11). miRNAs originating from breast tumors can also enhance the invasion of breast cancer cells across the blood-brain barrier by compromising the integrity of brain microvascular endothelial cells (11). Khan et al.provided a comprehensive review of the current literature on miRNAs derived from breast cancer that promote BCBM, detailing their roles in the intricate processes of BCBM, their

Antibody–drug conjugates (ADCs) have garnered significant attention as an innovative therapeutic strategy in cancer treatment. The mechanism of action for ADCs involves the targeted delivery of antibodies to specific receptors, followed by the release of cytotoxic payloads directly into tumor cells. In recent years, ADCs have made substantial progress in the treatment of breast cancer (BC), particularly demonstrating significant efficacy in the human epidermal growth factor receptor-2 (HER-2)-positive subgroup. Clinical evidence indicates that ADCs have notably improved treatment efficacy and survival outcomes for BC patients. However, challenges such as drug toxicities and the emergence of drug resistance necessitate further research and discussion. In this paper, we will summarize the advances in ADCs targeting various receptors in BC patients and explore the challenges and future directions in this field. We anticipate that the increasing availability of ADCs will lead to more effective and personalized treatment options for BC patients.

Human trophoblastic cell surface antigen 2 (Trop2) is a glycoprotein, a cellular marker of trophoblastic and stem cells, and a calcium signaling transducer involved in several signaling pathways, leading to the proliferation, invasion, and metastasis of tumors. It is expressed at a low level in normal epithelial cells, but at a high level in many tumors, making it an ideal target for cancer therapy. According to previous literature, Trop2 is broadly expressed in all breast cancer subtypes, especially in triple negative breast cancer (TNBC). Several clinical trials have demonstrated the effectiveness of Trop2-targeted therapy in breast cancer. Sacituzumab govitecan (SG) is a Trop2-targeted antibody-drug conjugate (ADC) that has been approved for the treatment of metastatic TNBC and hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This article reviews the structure and function of Trop2, several major Trop2-targeted ADCs, other appealing novel Trop2-targeted agents and relevant clinical trials to provide a landscape of how Trop2-targeted treatments will develop in the future.

Many geminiviruses including members of the genus Begomovirus produce a protein known as C4 or AC4. Whereas C4/AC4 typically consists of over 80 amino acid residues, a few are much shorter. The significance of these shorter C4/AC4 proteins in viral infection and why the virus maintains their abbreviated length is not yet understood. The AC4 of the begomovirus tomato leaf curl Hsinchu virus (ToLCHsV) contains only 65 amino acids, but it extends to 96 amino acids when the natural termination codon is replaced with a normal codon. We discovered that both interrupting and extending AC4 were harmful to ToLCHsV. The extended AC4 (EAC4) also showed a lower ability to promote the infection of the heterologous virus potato virus X than the wildtype AC4. When the wildtype AC4 was fused with yellow fluorescent protein (AC4-YFP), it was predominantly found in chloroplasts, whereas EAC4-YFP was mainly localized to the cell periphery. These results suggest that ToLCHsV's AC4 protein is important for viral infection, and the virus may benefit from its abbreviated length because it may lead to chloroplast localization.

Background: According to previous literatures, plasma thioredoxin reductase (TrxR) level was significantly elevated in various malignant tumors and serve as a potential biomarker for diagnosis and prognostic prediction. However, there is little awareness of the clinical value of plasma TrxR in gynecologic malignancies. In the present study, we aim to evaluate the diagnostic accuracy of plasma TrxR in gynecologic cancer and explore its role in treatment surveillance. Methods: We retrospectively enrolled 134 patients with gynecologic cancer and 79 patients with benign gynecologic disease. The difference of plasma TrxR activity and tumor markers level between two groups was compared using Mann-Whitney U test. By detecting pretreatment and post-treatment level of TrxR and conventional tumor markers, we further assessed the change trend of them with the Wilcoxon signed-ranks test. Results: Compared with benign control [5.7 (5, 6.6) U/mL], statistically significant increase of TrxR activity was observed in gynecologic cancer group [8.4 (7.25, 9.825) U/mL] ( P < .0001), regardless of age and stage. On the basis of receiver operating characteristic (ROC) curves, we found plasma TrxR shows the highest diagnostic efficacy for distinguishing malignancy with benign disease, with an area under the curve (AUC) of 0.823 (95% confidence interval [CI] = 0.767-0.878), in the whole cohort. Besides, patients receiving treatment previously [8 (6.5, 9) U/mL] had a decreased TrxR level relative to treatment-native patients [9.9 (8.6, 10.85) U/mL]. Furthermore, follow-up data showed that plasma TrxR level would be evidently decreased after two courses of antitumor therapy ( P < .0001), which is consistent with the downward trend of conventional tumor markers. Conclusion: Collectively, all these results demonstrated plasma TrxR is an effective parameter for gynecologic cancer diagnosis and concurrently acts as a promising biomarker for treatment response assessment.