crossing96/oncoscreening huggingface dataset:
Comparative efficacy and safety of tislelizumab and other programmed cell death protein 1 inhibitors in first-line treatment of advanced gastroesophageal cancers: a systematic review and network meta-analysis.	BACKGROUND: Several programmed cell death protein-1 inhibitors are approved for the first-line treatment of advanced gastric/gastroesophageal junction cancer, including pembrolizumab, nivolumab and, more recently, tislelizumab. Since direct comparisons between these agents are lacking, advanced statistical modeling can be utilized to evaluate the relative efficacy and safety of tislelizumab compared with other first-line immunotherapy regimens in this indication. METHODS: A systematic literature review was performed to identify and summarize published randomized controlled trials investigating first-line treatments in adult patients with unresectable, locally advanced, or metastatic human epidermal growth factor receptor 2-negative gastric/gastroesophageal junction cancer. Relevant trials were synthesized using a Bayesian network meta-analysis; fixed-effect models were conducted for all analyses. The network meta-analysis base case used the intent-to-treat populations for tislelizumab + chemotherapy and placebo + chemotherapy from RATIONALE-305. RESULTS: Key comparators included nivolumab + chemotherapy (ATTRACTION-4, CheckMate 649), and pembrolizumab + chemotherapy (KEYNOTE-062, KEYNOTE-859). Tislelizumab + chemotherapy demonstrated similar efficacy compared with nivolumab + chemotherapy and pembrolizumab + chemotherapy for both overall survival and progression-free survival. Tislelizumab + chemotherapy was associated with significantly lower odds of grade ≥ 3 treatment-related adverse events compared with nivolumab + chemotherapy, and there were no statistically significant differences between tislelizumab + chemotherapy compared with pembrolizumab + chemotherapy. CONCLUSION: Overall, these analyses suggest that tislelizumab + chemotherapy is similarly efficacious to pembrolizumab + chemotherapy and nivolumab + chemotherapy, and is associated with a similar or lower incidence of grade ≥ 3 treatment-related adverse events in the first-line treatment of gastric/gastroesophageal junction cancer.	esophagus
SHIP2-PLK1 crosstalk promotes sensitivity to dual inhibition in esophageal squamous cell carcinoma.	BACKGROUND: Drug synergy in cancer therapy has gained attention for its potential to enhance efficacy and minimize adverse effects. Synergy, where the combined effect of drugs exceeds the sum of their individual effects, is beneficial in addressing tumor heterogeneity and drug resistance in oncology. Esophageal squamous cell carcinoma (eSCC), accounting for over 85% of esophageal cancer cases, has a poor prognosis and limited therapeutic options. Targeted therapies have shown inefficiency in eSCC due to resistance mechanisms, making drug combination an interesting option. METHODS: To investigate new therapeutic startegies in eSCC, we utilized a combination of multiple human eSCC cell lines, xenotransplant models, primary mouse eSCC model, CRISPR/Cas9-based genetic manipulation and RNA sequencing analysis. RESULTS: We report the role of SHIP2, a phosphoinositide (PI) 5-phosphatase, in eSCC. Amplification of the INPPL1 gene, encoding SHIP2, was prevalent in eSCC, linked to elevated SHIP2 transcript levels. SHIP2 knockdown and pharmacological inhibition demonstrated its influence on eSCC cell survival, proliferation, and adhesion, partially by decreasing AKT phosphorylation and perturbing cell cycle-associated transcripts. SHIP2's impact was not restricted to cells harboring INPPL1 amplification, implying its potential activity across diverse eSCC subtypes. Compensation mechanisms emerged in SHIP2-deficient eSCC cells, highlighting the necessity of combinatory approaches to counteract resistance. RNA sequencing identified PLK1 as a prominent downregulated transcript upon SHIP2 inhibition, revealing synergistic potential with PLK1 inhibitors. CONCLUSIONS: Our data support the use of specific SHIP2 inhibitors, in combination with PLK1 inhibitors, as a promising strategy for stalling eSCC growth, amplifying treatment response, and circumventing resistance. This study unravels the intricate interplay of SHIP2 within the PI3K/AKT pathway and cell cycle in eSCC, paving the way for targeted interventions with the potential to transform the therapeutic landscape of this challenging malignancy.	esophagus
Chemoprevention in Barrett's Esophagus: An Updated Review.	Barrett's esophagus is a premalignant condition that significantly increases the risk of esophageal Adenocarcinoma (EAC), a rapidly rising cancer in developed countries. Given the limitations of surveillance in preventing EAC-related mortality, chemoprevention has emerged as a potential strategy to reduce disease progression. Proton pump inhibitors are the cornerstone of chemoprevention, reducing acid reflux, and inflammation, with studies like the Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia trial suggesting added benefits when combined with aspirin. nonsteroidal antiinflammatory drugs, particularly aspirin, inhibit COX-2, a key enzyme in carcinogenesis, showing promise in reducing EAC risk despite concerns about gastrointestinal bleeding.	esophagus
Increased IgG4 expression within tertiary lymphoid structures of esophageal cancer and implications for prognosis.	BACKGROUND: Tertiary lymphoid structures (TLS) have been observed in various tumors, including esophageal squamous cell carcinoma (ESCC), where they function as active centers of humoral immunity within the tumor microenvironment, facilitating the production of distinct immunoglobulin (Ig) subtypes with diverse effects. This study aimed to investigate the expression of TLS-associated Ig in ESCC and its prognostic significance. METHODS: A retrospective analysis was conducted on 109 ESCC cases. TLS presence was evaluated using immunohistochemistry, and the expression of Ig-positive cells was assessed. Additionally, gene expression profiles related to TLS were analyzed with gene chip data from 274 ESCC cases obtained from the GEO database. RESULTS: Among the 109 ESCC cases, 69 (63.3%) exhibited TLS, while 40 (36.7%) did not. Patients with TLS demonstrated significantly better prognoses compared to those without TLS (P < 0.001). ESCC tumor tissues with TLS exhibited higher infiltration of Ig-positive immune cells. Among the variables examined, the differential expression of IgG4 was the most pronounced (P = 0.04). Furthermore, ESCC cases exhibiting TLS with elevated IgG4 expression demonstrated a poorer prognosis compared to those with TLS and reduced IgG4 expression (P = 0.036). The presence of TLS in general and low IgG4 expression in TLS were associated with improved survivals in patients who underwent post-surgery chemotherapy (p < 0.001 and p = 0.001, respectively). Analysis of the GEO dataset indicated that predominant IgG4 expression within TLS was associated with a reduced number of activated CD8+ T cells and an increased presence of CD4+ T helper cells and dendritic cells. The expression of TLS in ESCC was linked to a more favorable prognosis, whereas TLS with increased IgG4 expression correlated with a less favorable prognosis. CONCLUSIONS: The differential expression of immunoglobulins within TLS can modulate its function within the tumor microenvironment. In addition to the number of TLSs themselves, the immune heterogeneity present within TLS maybe a critical factor in individualized assessment of tumor immunotherapy.	esophagus
TRIM21 knockdown suppresses ESCC progression and induces autophagy-mediated apoptosis via AKT/mTOR signaling pathway.	Esophageal squamous cell carcinoma (ESCC) is a prevalent digestive tract malignancy characterized by high morbidity and mortality. Tripartite motif-containing protein 21 (TRIM21), a key regulator of innate immunity, has been implicated in the development of several cancers. However, its role in ESCC progression remains largely elusive. In this study, we identified TRIM21 as an oncogene promoting ESCC progression. Analysis of TCGA database revealed significant TRIM21 upregulation in ESCC tissues. In vitro, silencing TRIM21 markedly inhibited ESCC cell migration and invasion. Furthermore, TRIM21 downregulation substantially reduced cellular proliferation, associated with G1 phase cell cycle arrest and decreased CDK4/6 expression. We also observed that TRIM21 silencing significantly induced autophagy. This was evidenced by increased expression of autophagy-related markers (LC3B, Atg12, Beclin-1) and a higher number of autophagosomes and autolysosomes. Accompanied by autophagy, the apoptotic protein cleaved PARP1 (Cl. PARP1) in TRIM21 knockdown cells was raised. While the cells were treated with chloroquine (CQ), an autophagy inhibitor, the expression of Cl. PARP1 in the TRIM21 knockdown group was reduced compared to its control group. Mechanistically, TRIM21 loss inhibited the AKT/mTOR signaling pathway, thereby regulating cell growth and inducing autophagy-mediated apoptosis. Collectively, our findings provide novel insights into the role of TRIM21 in ESCC and offer a potential therapeutic target for ESCC.	esophagus
CAR T cells targeting B7H3 demonstrate potent preclinical activity against AML and ESCC.	T cells engineered to express chimeric antigen receptors (CARs) are a promising modality to treat refractory cancers. CD19 CAR-T therapy has achieved remarkable responses in against B-cell lymphomas, however, challenges persist for acute myeloid leukemia (AML) and solid malignancies. B7H3 is an immune regulatory molecule that is highly expressed in various tumor cells. Its abnormal expression in acute AML and esophageal squamous cell carcinoma (ESCC) is closely related to tumor progression. Here, we describe B7H3-targeted CAR-T cells constructed using the single-chain variable fragment (scFv) of an anti-B7H3 antibody and systematically evaluated their safety and efficacy in vitro and in mice models of AML and ESCC. Based on the monoclonal antibody targeting B7H3, namely A172 which screened according to phage antibody display library technology, we undertook humanization of the A172 antibody, resulting in A172-hu4, and further verified its affinity and cytotoxicity in the cell lines of AML and ESCC. The resulting A172-hu4-CAR-T displayed strong IFN-γ and IL-2 production and cytotoxic effects in vitro. We also identify that A172-hu4-CAR-T treatment could lead to more pronounced tumor suppression in AML and ESCC xenograft mouse models with no obvious toxic reactions to mice main organs. Accordingly, this study provides a novel target for CAR-T therapy in AML and ESCC to promote the development of clinical treatment strategies.	esophagus
Single-Cell RNA-Seq Reveals the Effect of Commensal Bacteria on the Multistep Development of Esophageal Cancer.	Microbiomes within the tumor microenvironment (TME) are intricately linked to the modulation of cancer cell properties and the prognoses of various types of cancer, including esophageal squamous cell carcinoma (ESCC). However, their contribution to the onset and advancement of ESCC is still not fully elucidated. We adopted single-cell RNA sequencing to investigate the effects of esophageal commensal bacteria during the development of mice's spontaneous ESCCs. By analyzing the single-cell transcriptomes of 54,562 cells across different ESCC pathological stages, commensal bacteria were observed to display a cellular heterogeneous distribution in the ESCC TME. These bacteria were associated with the malignant transformation of epithelial cells and the formation of inflammatory fibroblasts, contributing to a chronic inflammatory microenvironment. However, after depriving commensal bacteria with an antibiotic cocktail (ABX), infiltrations of inflammatory fibroblasts and anti-bacteria macrophages were lower than those in the control H(2)O group, while the infiltration of regulatory Cd4(+) T (Treg) cells was higher. Interactions between inflammatory fibroblasts and Treg cells were intensified in the ABX group, which exacerbated the immunosuppressive state in the TME and developed more invasive carcinomas. This study demonstrates the significant role of commensal bacteria in ESCC tumorigenesis and sheds light on the potential clinical applications of adjusting commensal bacteria for the prevention and treatment of ESCC.	esophagus
Piperine targets SOAT1 to inhibit the progression of esophageal squamous cell carcinoma via ferroptosis.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major contributor to cancer-associated mortality worldwide. Therefore, there is an urgent need to identify novel therapeutic targets and treatment modalities for this disease. Piperine, a natural alkaloid, has been shown to possess notable anticancer properties. However, the anticancer efficacy of piperine in ESCC and its underlying molecular mechanisms remain unclear. PURPOSE: This study aimed to investigate the anticancer effect and molecular mechanism of piperine in ESCC. METHODS: To evaluate the anticancer potential of piperine against ESCC, a series of experiments was conducted. These included key gene knockdown, CCK-8 assays, colony formation tests, molecular docking studies, bioinformatics analyses, Western blotting, and real-time PCR arrays. RESULTS: Piperine inhibited cell proliferation, migration, and invasion. Importantly, piperine was identified as a potential Sterol O-acyltransferase 1 (SOAT1) inhibitor. Interestingly, piperine targets SOAT1 to enhance ferroptosis and inhibit cell viability. Furthermore, piperine targets SOAT1 to synergistically enhance the anticancer effects of cisplatin in ESCC. Further data analysis showed that inhibiting SOAT1 increased KLF4-induced ALOX12B expression by decreasing the PI3K-AKT pathway. Finally, in vivo studies demonstrated that the SOAT1 inhibitor piperine hindered tumor growth in mice without altering body weight. CONCLUSION: This study is the first to demonstrate that piperine targets SOAT1 to enhance ferroptosis by inhibiting the PI3K-AKT axis and upregulating the expression of KLF4/ALOX12B. This study strongly emphasizes the potential of piperine as a promising clinical therapeutic candidate for ESCC.	esophagus
Beamion BCGC-1: phase Ib/II trial of zongertinib for advanced HER2-positive breast or gastroesophageal cancers.	BACKGROUND: Overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) is a recognized oncogenic driver in metastatic breast cancer (mBC) and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinomas (mGEAC). Although HER2-directed monoclonal antibodies, antibody - drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of HER2-positive tumors, additional combination regimens and/or novel agents are needed to expand sequential therapy options and improve patient outcomes - particularly following treatment with trastuzumab deruxtecan (T-DXd). Zongertinib is a novel, irreversible, HER2-selective TKI that spares EGFR. STUDY DESIGN: Here, we detail the rationale and design of Beamion BCGC-1 (NCT06324357), an international Phase Ib/II open-label trial in which patients with previously treated HER2-positive mBC or mGEAC will receive zongertinib alone or in combination. Phase Ib (dose escalation) will determine the maximum tolerated dose of zongertinib plus trastuzumab emtansine (T-DM1), T-DXd, or trastuzumab ± capecitabine, in patients with HER2-positive mBC, and plus T-DXd in patients with HER2-positive mGEAC. Phase II (dose optimization) will assess two doses of zongertinib in combination regimens, or as monotherapy, in patients with mBC or mGEAC. The trial is actively recruiting in six countries globally. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT06324357.	esophagus
Multi-cohort validation based on coagulation-related genes for predicting prognosis of esophageal squamous cell carcinoma.	OBJECTIVE: In malignant tumors, a hypercoagulable state is frequently observed and is intricately intertwined with cancer development and the remodeling of the immune microenvironment. Recently, the coagulation-related genes (CRGs) signature has emerged as highly significant for the prognosis and immunotherapy of patients with various cancers. Nevertheless, their application in esophageal squamous cell carcinoma (ESCC) remains uninvestigated. Here, our objective is to explore the role of the CRGs signature in forecasting prognosis and predicting patient's response to immunotherapy. METHODS: According to the prognostic CRGs, consensus clustering was utilized to stratify ESCC patients in the GSE53625 cohort into two subgroups. Subsequently, difference analysis and univariate cox analysis were conducted on the two subgroups, and a CRGs signature was constructed by leveraging these genes. Next, multiple RNA transcriptome cohorts were utilized to validate the signature. Moreover, functional enrichment, tumor mutation burden (TMB), tumor infiltration, immune function, and immunotherapy response of this signature were investigated. RESULTS: A CRGs signature composed of six genes (PTX3, CILP, CFHR4, SULT1B1, IL5RA, and FAM151A) was constructed. This signature serves as an independent and reliable prognostic factor. Additionally, when compared with the 32 prognostic signatures previously reported, the CRGs signature exhibited superior performance in the ESCC prognostic cohorts. Additionally, we found that high-risk ESCC exhibited higher immune infiltration, lower TMB, higher TIDE, and a lower proportion of immunotherapy response. In vitro experiments have shown that the gene SULT1B1, which exhibits the highest accuracy in predicting tumor status, significantly inhibited the proliferation and metastasis. CONCLUSIONS: We constructed and validated a robust CRGs signature. Moreover, as one of the model CRGs, the tumor-suppressive role of SULT1B1 in ESCC was experimentally verified in vitro. These results provide novel insights into enhancing the prognosis of ESCC and formulating treatment strategies.	esophagus
Cancer-derived fucosylated exosomal miR-6842-3p as a novel marker promotes ESCC angiogenesis and metastasis via the PTEN/AKT/mTOR/IRF1/CXCL10 axis.	Tumour-derived fucosylated exosomes (FUC-Exo) play significant roles in cancer progression. However, the functions and mechanisms of fucosylated exosome-derived miRNAs in oesophageal squamous cell carcinoma (ESCC) remain largely unknown. Using lentil lectin (LCA)-coated magnetic beads for FUC-Exo isolation, small RNA sequencing and RT-qPCR identified miR-6842-3p as a novel ESCC biomarker. In vitro and in vivo assays explored its oncogenic role and pro-angiogenic function. Dual-luciferase assays, ChIP-qPCR, western blot and rescue assays were performed to elucidate angiogenic mechanisms. miR-6842-3p is upregulated in ESCC tissues and serum FUC-Exo, significantly associated with advanced clinical stages, worse prognosis and serves as an early diagnostic biomarker for ESCC. miR-6842-3p acts as an oncogene, promoting tumour growth, metastasis and angiogenesis in ESCC. Tumour-derived fucosylated exosomal miR-6842-3p, when internalised by HUVECs, downregulates PTEN, triggering the phosphorylation of AKT and mTOR. This is followed by the inhibition of IRF1 expression, thereby downregulating CXCL10 expression and driving angiogenesis. These findings elucidate that miR-6842-3p functions as a key driver of ESCC growth, metastasis and angiogenesis. Fucosylated exosomal miR-6842-3p promotes angiogenesis by mediating the PTEN/AKT/mTOR/IRF1/CXCL10 axis, highlighting its potential as a novel biomarker and therapeutic target for ESCC.	esophagus
Neoadjuvant Immuno-Chemotherapy Versus Neoadjuvant Chemoradiotherapy in Locally Advanced Oesophageal Squamous Cell Carcinoma.	OBJECTIVES: The chemoradiotherapy for oesophageal cancer followed by surgery study (CROSS) regimen has been the standard neoadjuvant treatment for oesophageal squamous cell carcinoma over the last decade. However, the emerging Neoadjuvant Immuno-Chemotherapy followed by Esophagectomy (NICE) regimen has shown promising potential. This study compares the treatment response and the long-term outcomes of NICE versus CROSS for oesophageal squamous cell carcinoma. METHODS: We retrospectively analysed patients who underwent the NICE or the CROSS regimen between January 2018 and April 2022. NICE comprised camrelizumab with carboplatin and paclitaxel over two 21-day cycles. CROSS included carboplatin and paclitaxel chemotherapy with concurrent radiotherapy (41.4 Gy) per protocol. After matching, 177 patients were included in each group for analysis. RESULTS: The pathological complete remission (pCR) rates were similar between the NICE and the CROSS (20.9% vs 25.4%, P = .314) regimens. NICE demonstrated superior 3-year overall survival (73.5% vs 58.4%, P = .003) and cancer-specific survival (77.3% vs 64.3%, P = .006). Recurrence rates, including local and distant recurrences, were comparable. Subgroup analysis revealed no survival differences in patients with a pCR (hazard ratio 1.65, 95% CI 0.56-4.84), but patients without non-pCR in the NICE group showed improved overall survival compared to those in the CROSS (hazard ratio 1.86, 95% CI 1.24-2.77) group. Patients following NICE reported higher proportions of adjuvant therapy than those following CROSS (P < .001) and were largely driven by immunotherapy (OR 5.45). Furthermore, in multivariable analysis, receipt of adjuvant therapy was identified as a significant promoter for improving long-term prognosis after NICE. CONCLUSIONS: NICE offers better survival than CROSS with similar recurrence patterns. Adjuvant immunotherapy might be an important factor for long-term benefits in residual pathological disease after NICE.	esophagus
Organ preservation in esophageal cancer treatment, is it time now?	"As esophageal cancer (EC) is a prevalent malignancy of the digestive tract, with esophageal squamous cell carcinoma being its predominant pathological subtype, accounting for nearly 90% of all cases. Current treatment modalities for EC include surgery, chemotherapy, and radiotherapy; however, single-modality therapies are associated with inherent limitations. Advances in endoscopic techniques and the integration of immunotherapy have enhanced the feasibility and safety of organ-preserving strategies for EC. These approaches enable patients to achieve prolonged survival and an improved quality of life. Nevertheless, the criteria for selecting patients suitable for organ preservation require further refinement through active surveillance. The optimal timing for surgical intervention in patients with tumor progression or metastasis remains controversial; however, the ""watch and wait"" strategy may represent a viable option for selected individuals."	esophagus
Precision Antibody Therapy in Gastric and Gastroesophageal Cancer: Targeting FGFR2b, CLDN18.2, and VEGFR2.	Gastric and gastroesophageal junction (G/GEJ) adenocarcinomas remain among the most aggressive and lethal malignancies globally. Most patients are diagnosed at advanced stages and respond poorly to conventional chemotherapy, highlighting the urgent demand for more effective, novel treatment strategies such as monoclonal antibody therapies targeting drivers of tumor progression. This review examines the mechanisms, safety profiles, and clinical trial outcomes of three targeted agents-bemarituzumab, zolbetuximab, and ramucirumab-which inhibit tumor growth through the FGFR2b, CLDN18.2, and VEGFR2 pathways, respectively. We also compare traditional versus adaptive clinical trial designs, explore emerging challenges such as therapeutic resistance and treatment-related toxicities, and consider implications for personalized medicine. Collectively, these agents represent a paradigm shift from empiric chemotherapy toward biomarker-driven immunotherapy, with the potential to significantly improve survival and quality of life in patients with advanced G/GEJ cancers.	esophagus