Huaimin Liu

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor with poor clinical outcomes and limited treatment options. Dingxiang Guanshitong (DGST), a traditional Chinese herbal formulation, has shown potential activity in ESCC, but its molecular mechanisms require further clarification. The current study aimed to evaluate the therapeutic impact and underlying biological actions of DGST on ESCC. Network pharmacology was used to identify candidate DGST constituents and targets, followed by KEGG pathway enrichment analysis. Antitumor effects of DGST was examined in a 4-nitroquinoline 1-oxide (4NQO)-induced ESCC mouse model using H&E staining, immunohistochemistry, TUNEL assay, and flow cytometry. Proteomics analysis identified differentially expressed proteins and enriched pathways. In TE-1 cells, TAK1 knockdown/overexpression stable lines were constructed by lentiviral transduction, and pathway involvement was evaluated using immunofluorescence, luciferase reporter assays, CCK-8, Transwell, scratch assays, qRT-PCR, western blotting, and metabolic indicator assays. DGST showed dose-associated suppression of ESCC tumor progression, cell proliferation, migration, and invasion, while promoting apoptosis. Proteomics suggested that DGST affected glycolysis and NF-κB-related pathways. DGST treatment was associated with reduced phosphorylation of TAK1, IκBα, and p65, lower GLUT1, HK2, PFKP, and LDHA expression, decreased ATP levels, and increased MPC1 as well as mitochondrial complex indicators. TAK1 knockdown enhanced the effects of DGST, whereas its overexpression reversed these effects. DGST may inhibit ESCC progression by modulating TAK1/NF-κB/GLUT1 axis-mediated glycolytic reprogramming. The findings elucidate the potential therapeutic value of DGST in the treatment of ESCC and provide mechanistic insights for its clinical application.

Objective: To compare pathological complete response (pCR) across different neoadjuvant treatment strategies in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and to identify clinicopathological factors associated with pCR. Methods: In this single-center retrospective cohort study, 247 consecutive patients with locally advanced ESCC who underwent neoadjuvant therapy followed by radical esophagectomy between January 2024 and June 2025 were included. Patients were categorized into four treatment groups: chemotherapy alone (CT, n = 50), chemoradiotherapy (CRT, n = 38), chemotherapy plus immunotherapy (CT+IO, n = 142), and chemoradiotherapy plus immunotherapy (CRT+IO, n = 17). Pathological complete response was defined as ypT0N0. Clinicopathological characteristics were compared using χ² or Fisher’s exact tests. Factors associated with pCR were evaluated using univariable and multivariable logistic regression analysis. Results: Overall, 63 patients (25.5%) achieved pCR. The pCR rate was lower in the CT group than in the CT+IO group (6.0% vs. 26.8%). After adjustment for potential confounders, chemotherapy alone remained associated with lower odds of pCR than CT+IO (OR = 0.174, 95% CI, 0.046-0.658, P = 0.010). No significant differences were observed between CT+IO and either CRT or CRT+IO. Receipt of more than two neoadjuvant treatment cycles was associated with higher odds of pCR (OR = 2.764, 95% CI, 1.372-5.565, P = 0.004). Compared with cT3 disease, cT2 disease was associated with higher odds of pCR (OR = 3.049, 95% CI, 1.356-6.857, P = 0.007). Conclusions: Neoadjuvant treatment regimen, the number of neoadjuvant treatment cycles, and pretreatment clinical T stage were associated with pathological complete response in locally advanced ESCC. Chemotherapy alone was associated with lower odds of pCR than CT+IO, whereas receipt of more than two treatment cycles was associated with higher odds of pCR. These findings provide real-world evidence regarding factors associated with pathological response.

Cuproptosis is a type of cell death that depends on the energy production process inside cells, and it is important in cancer treatment. This study aimed to identify cuproptosis‐associated genes in triple‐negative breast cancer (TNBC) and reveal regulatory pathways. We applied weighted gene co‐expression network analysis to screen gene expression data from TNBC patients. Cuproptosis‐associated genes were identified at the intersection of the co‐expression modules and the cuproptosis gene dataset. G protein‐coupled receptor 68 (GPR68) was identified as a cuproptosis‐associated gene that is highly expressed in TNBC cells. Knockdown of GPR68 inhibited TNBC cell growth, migration, and invasion. The knockdown of GPR68 enhanced cuproptosis in TNBC cells when stimulated with ES‐Cu, leading to an accumulation of cellular copper. This effect was reversed by the copper chelator tetrathiomolybdate. Correlation analysis verified that GPR68 regulates glutaminase (GLS) expression in TNBC cells. GLS knockdown reversed the promoted role of GPR68 in TNBC progression and the inhibitory role of GPR68 in TNBC cell cuproptosis. We further investigated the role of GPR68 in TNBC through pathway enrichment analysis, which revealed significant enrichment in the mitogen‐activated protein kinase (MAPK) signaling pathway. GPR68 overexpression increased the levels of ERK phosphorylation. The ERK signaling pathway inhibitor, Trametinib, blocked the effects of GPR68 on TNBC progression and cuproptosis. GPR68 knockdown hindered TNBC development and induced cell cuproptosis by regulating the MEK/ERK signaling pathway, which is linked to GLS. This study provides new insights into developing cuproptosis targets for TNBC treatment.

Background: The development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) dramatically altered the treatment for non-small cell lung cancer (NSCLC). The implementation of comprehensive genomic profiling for NSCLC facilitates to identify more uncommon genetic alterations in EGFR. S768I and V769L are two rare mutations in exon 20 of EGFR. However, the clinical reactivity of afatinib to the S768I/V769L compound mutation remains controversial, and there are no reports on whether osimertinib is effective against S768I/V769L. This case study aims to describe a clinical experience with these mutations, detailing the therapeutic strategy adopted and its outcomes, alongside a literature review to understand the broader implications for treatment. Case presentation: A 47-year-old man was referred to the Affilated Cancer Hospital of Zhengzhou University due to dry cough for more than 2 months and was diagnosed with Stage IIIB (T1cN3M0) lung adenocarcinoma. Mutation analysis of 26 lung cancer-related genes was performed using pathological tissue sample by targeted next-generation sequencing. A compound mutation of S768I and V769L in epidermal growth factor receptor exon 20 were observed. After multi-disciplinary treatment, the patient received concurrent chemoradiotherapy with pemetrexed and cisplatin, and achieved partial response. This patient did not receive durvalumab immunoconsolidation therapy for economic reasons. He developed disease progression 6 months after the end of radiotherapy. The patient was treated with afatinib at 40 mg daily by oral administration from January 2023. At the 1-month response assessment, the primary tumor in the right lung shrank and remained stable for 13 months. Magnetic resonance imaging revealed multiple nodules with brain metastases. We performed NGS testing of peripheral blood, and no mutation was found. Considering the superior intracranial efficacy of osimertinib, we tried high dose osimertinib for the patient. He achieved partial response after 15 days, and there were no intolerable adverse reactions. Three months later, the intracranial metastasis progressed, and headache appeared. The patient was switched to whole brain radiotherapy. The intracranial metastases remained stable after radiotherapy. The patient died 3 months later due to the progression of intracranial metastasis. overall survival was 26 months, slightly poorer than anticipated for patients with single driver gene mutations. Conclusion: The S768I/V769L mutation should be considered a poor-prognosis compound mutation. Patients with EGFR S768I/V769L compound mutated NSCLC may benefit from afatinib and osimertinib. Drugs with strong brain penetration capabilities are still needed for patients with S768I/V769L compound mutation to further improve survival outcomes.

Background Breast cancer poses a significant threat on human health. Rhizoma Dioscoreae (RD), a traditional Chinese medicinal herb, has shown positive effect in breast cancer treatment; however, the underlying molecular mechanisms remain unknown. Methods We identified the active pharmaceutical ingredients (APIs) in RD and their potential targets using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Targets related to breast cancer were gathered from GeneCards and Online Mendelian Inheritance in Man (OMIM) database. We constructed RD API-gene interaction network using Cytoscape software. Protein-protein interaction (PPI) data were obtained from the Search Tool for the Retrieval of Interacting Genes (STRING) database. Key APIs and hub genes were screened via network topological parameters. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) pathway enrichment analyses were conducted. Molecular docking and in vitro experiments were performed to validate our network pharmacology findings. Results We identified 12 APIs in RD and 28 genes overlapped between RD and breast cancer. Molecular docking showed stable binding between key ingredients and hub genes. Stigmasterol and diosgenin served as the most critical APIs. Further experimental findings demonstrated that RD inhibited breast cancer via downregulating HIF-1α, RELA, VEGFA, PGR, and NCOA1, critical in tumor angiogenesis and hormone-mediated signaling. Conclusion RD might inhibit breast cancer angiogenesis and hormone-mediated oncogenesis by downregulating HIF-1α, RELA, VEGFA, PGR, and NCOA1, which provides more evidence for the application of RD in the management of breast cancer.

Summary: Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell death modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which can be mediated by multifaceted PANoptosome complexes assembled via integrating components from other cell death modalities. There is growing interest in the process and function of PANoptosis. Accumulating evidence suggests that PANoptosis occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, and cancer. Given the impact of PANoptosis across the disease spectrum, this review briefly describes the relationships between pyroptosis, apoptosis, and necroptosis, highlights the key molecules in PANoptosome formation and PANoptosis activation, and outlines the multifaceted roles of PANoptosis in diseases together with a potential for therapeutic targeting. We also discuss important concepts and pressing issues for future PANoptosis research. Improved understanding of PANoptosis and its mechanisms is crucial for identifying novel therapeutic targets and strategies.

With the increasing incidence of esophageal cancer, its diagnosis and treatment have become one of the key issues in medical research today. However, the current diagnostic and treatment methods face many unresolved issues, such as low accuracy of early diagnosis, painful treatment process for patients, and high recurrence rate after recovery. Therefore, new methods for the diagnosis and treatment of esophageal cancer need to be further explored, and the rapid development of nanomaterials has brought new ideas for solving this problem. Nanomaterials used as drugs or drug delivery systems possess several advantages, such as high drug capacity, adjustably specific targeting capability, and stable structure, which endow nanomaterials great application potential in cancer therapy. However, even though the nanomaterials have been widely used in cancer therapy, there are still few reviews on their application in esophageal cancer, and systematical overview and analysis are deficient. Herein, we overviewed the application of nanodrug systems in therapy and diagnosis of esophageal cancer and summarized some representative case of their application in diagnosis, chemotherapy, targeted drug, radiotherapy, immunity, surgery and new therapeutic method of esophageal cancer. In addition, the nanomaterials used for therapy of esophageal cancer complications, esophageal stenosis or obstruction and oesophagitis, are also listed here. Finally, the challenge and the future of nanomaterials used in cancer therapy were discussed.