Esophageal Squamous Cell Carcinoma

OS subgroup analysis showed comparable treatment effect by TAP score at 10% cutoff, CPS at cutoff 10, and TC score at 1% cutoff. TAP score and CPS at these cutoffs exhibited substantial concordance. Results indicate that the quicker, visually estimated TAP score and CPS may be interchangeable for clinical measurement of PD-L1 expression in patients with ESCC.

miR-16-5p may promote the proliferation, migration, and invasion of ESCC through modulating AMPK/mTOR signaling pathway.

Trajectory analysis and flow cytometry revealed that DN B cells highly expressed genes involved in the antigen processing and presentation pathway, such as HLA-DR. The abundance of DN B cells and LMAs in ESCC provides novel potential targets for optimal immunotherapy against ESCC.

They might be the potential biomarkers for ESCC stage diagnosis. This study identified three novel miRNA markers potentially related to the diagnosis of ESCC and participated in the occurrence and development of ESCC through cell cycle, proteoglycans in cancer, p53 signaling pathway, protein digestion and absorption, transcriptional dysregulation in cancer, and signaling pathway for oocyte meiosis.

Our study has identified CCNG1 as a key regulator of radiosensitivity in ESCC, mediated through its interaction with the Wnt/β-catenin signaling pathway. Targeting the Wnt/β-catenin/CCNG1 axis presents a promising therapeutic strategy to enhance the efficacy of radiotherapy in ESCC, potentially overcoming radioresistance and improving patient outcomes.

In vivo, ML385 also promoted the killing effect of radiation on xenografted tumours in nude mice. This study identifies NRF2 inhibitor ML385 as a radiosensitizer of ESCC, which highlights the therapeutic potential of the NRF2-SLC7A11 pathway and provides a deeper understanding of the mechanism of ferroptosis in esophageal squamous cell carcinoma.

Furthermore, bifonazole exhibited antitumor effects on ESCC patient-derived xenograft (PDX) models by decreasing RRM2 expression and the dNTP pool. In summary, this study reveals the interaction network among HuR, RRM2, and bifonazole and demonstrated that bifonazole is a potential therapeutic compound for ESCC through inhibition of the HuR/RRM2 axis.

This prediction model showed favourable discrimination ability (area under the curve (AUC) was 0.913 (95% CI: 88.0 - 94.6) and a well-fitted calibration curve. We successfully established a long-term prognosis model for SESCC, which can be applied to effectively predict survival risks for patients, thus strengthening follow-up strategies.

FGF8 overexpression is an adverse independent prognostic factor in patients with upfront resected ESCC. Furthermore, FGF8 expression significantly correlates with ALK and EML4 amplification and may therefore qualify as a future therapeutic target.

P1, N=6, Recruiting, West China Hospital | Trial primary completion date: Oct 2024 --> Oct 2025

P2, N=35, Completed, Sun Yat-sen University

Drug screening with tumor organoids identifies that pinaverium bromide represses Smad3 activity and restrains Tgfbr2-deficient ESCC. Our studies provide a highly efficient platform to investigate the in vivo functions of ESCC-associated mutations and develop potential treatments for this miserable malignancy.

P2, N=28, Completed, Yonsei University | N=18 --> 28

P1, N=74, Recruiting, Peking University

P1, N=30, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2025 --> Jan 2025 | Trial primary completion date: Oct 2025 --> Jan 2025

Ultimately, the systemic immune-inflammation index was identified as an independent prognostic factor for overall survival. Additionally, the patients with no distant organ metastasis, or treated by first-line immunotherapy combined with concurrent chemoradiotherapy can considerably prolong survival. Inflammation is associated with the level of tumor infiltrating lymphocytes and that the systemic immune-inflammation index is an effective prognostic predictor for ESCC patients treated with ICIs.

To sum up, our findings imply that GPD1L may impede the initiation and advancement of ESCC via modulating the PI3K/AKT signaling pathway. GPD1L is considered to be a promising therapeutic target and biomarker to diagnose and treat ESCC.

P2, N=48, Active, not recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University | Recruiting --> Active, not recruiting

P1/2, N=250, Recruiting, Daiichi Sankyo | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=35, Recruiting, Peking University

P=N/A, N=32, Not yet recruiting, Jiangsu Province Hospital, the first affiliated hospital of Nanjing Medical University; Jiangsu Province Hospital, the first affiliated hospital of Na

P=N/A, N=5, Not yet recruiting, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

P=N/A, N=30, Recruiting, The First Affiliated Hospital of Zhengzhou University; The First Affiliated Hospital of Zhengzhou University

P4, N=180, Not yet recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P4, N=600, Not yet recruiting, Gaozhou People's Hospital; Gaozhou People's Hospital

P2, N=30, Recruiting, Beijing Cancer Hospital (Peking University Cancer Hospital and Institute); Peking University Cancer Hospital and Institute

P2, N=128, Not yet recruiting, Henan Cancer Hospital; Henan Cancer Hospital

P2, N=30, Recruiting, The First Affiliated Hospital of Zhengzhou University; The First Affiliated Hospital of Zhengzhou University

P1, N=92, Not yet recruiting, Jilin Cancer Hospital; Jilin Cancer Hospital

P1/2, N=187, Not yet recruiting, The first affiliated hospital, Zhejiang University School of Medicine; The first affiliated hospital, Zhejiang University School of Medicine

P2, N=51, Not yet recruiting, Hebei Medical University Fourth Hospital

P3, N=370, Active, not recruiting, BeiGene | Trial completion date: Dec 2024 --> Jun 2026 | Trial primary completion date: Nov 2024 --> Jun 2025

Pg infection in esophageal cancer blocked autophagosome-lysosome fusion in the tumor cells, thereby preventing Cx43 from lysosomal degradation and leading to chemoresistance of esophageal cancer.

Moreover, forkhead box M1 (FOXM1) was identified as a potential downstream target of NEK2 in the regulation of ESCC, with its overexpression reversing the effects of NEK2 knockdown on ESCC. Mechanistic studies also indicated that NEK2 may promote the malignant progression of ESCC by inhibiting cellular senescence through the activation of the FOXM1/c-Myc/p27 signaling pathways, which may provide a novel perspective for the management of ESCC.

Furthermore, the knockdown of AP001885.4 diminished histone lactylation and NF-κB (p65) expression, and the protein lactylation inhibitors (2-DG, 2-deoxy-D-glucose and oxamate) and the NF-κB inhibitor (JSH-23) also lessened c-myc expression. Consequently, our findings suggested that AP001885.4 promoted the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-κB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc.

However, the clinical significance of serum SIRT1 levels appears to differ from that of its tissue expression. Future research is required to clarify the role of serum SIRT1 in ESCC.

P3, N=432, Recruiting, Fudan University

P1, N=30, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=125 --> 30

Pharmacologic inhibition of NRF2 effectively improves radiosensitivity in nude mice. Collectively, our results strongly suggest that the ΔNp63α/PLEC/NRF2 axis plays a key role in radioresistance in ESCC, indicating that targeting NRF2 is a promising therapeutic approach for ESCC treatment.

The study highlights STAT1 as a core regulator in ESCC, directly influencing LHPP expression. The findings offer novel insights into the molecular mechanisms driving ESCC, shedding light on the cellular alterations and gene regulation dynamics within the ESCC microenvironment. This research provides a foundation for developing targeted therapeutic strategies, potentially utilizing the STAT1-LHPP axis as a focal point in ESCC treatment and prognosis.

P2, N=165, Recruiting, Sichuan University

Targeting CXCR4 with [64Cu]Cu-NOTA-CP01 for PET imaging of lymph nodes metastasis represents a promising approach that warrants further investigation. These findings have the potential to enhance diagnostic and therapeutic strategies for individuals with lymph nodes metastasis of ESCC.