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Review Open Access

Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review)

  • Authors:
    • Yueyue Li
    • Jingjing Li
    • Wenhui Mo
    • Xuanfu Xu
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Shidong Hospital, Shanghai 200438, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 120
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    Published online on: July 18, 2025
       https://doi.org/10.3892/or.2025.8953
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Abstract

The treatment of advanced esophageal squamous cell carcinoma (ESCC) presents numerous challenges. Whereas conventional therapies such as chemotherapy, radiotherapy and targeted treatments have achieved some success. However, the substantial heterogeneity of the disease poses challenges in achieving comprehensive therapeutic coverage through a single treatment approach, because molecular subtyping remains insufficiently defined. Consequently, the response rate to targeted therapies is limited. Moreover, the issue of resistance to immunotherapy is becoming increasingly prominent, and reliable predictive biomarkers are lacking. Additionally, the regulatory mechanisms of the tumor microenvironment in metastatic lesions require further investigation. In recent years, the advent of immunotherapy and novel drug development has brought new hope, particularly with the clinical application of antibody‑drug conjugates, bispecific antibodies, novel immune checkpoint inhibitors, new targeted therapies, and cell and vaccine therapies, which have markedly improved patient survival. The present review summarizes the current therapeutic landscape for advanced ESCC and discusses the potential of future treatment strategies. Despite improvements in survival rates with existing treatments, the integration of emerging therapies with precision medicine may become key to future ESCC management, through driving personalized treatment approaches and multidisciplinary collaboration, and ultimately improving patient quality of life and clinical outcomes.
View Figures

Figure 1

Treatment overview of advanced ESCC.
Comprehensive overview of the key therapeutic strategies for
advanced ESCC, encompassing traditional chemotherapy,
immunotherapy, targeted therapy, ADCs and emerging treatment
modalities. ADCs integrate targeted monoclonal antibodies with
cytotoxic agents and selectively deliver chemotherapy to cancer
cells. Immunotherapy and targeted therapy currently have numerous
highly effective and safe novel targets, thus enhancing immune
responses while disrupting tumor growth pathways. Additionally,
dual-specificity antibodies, cellular therapies and vaccine-based
approaches are under active development. Emerging directions
include personalized treatment regimens based on genetic profiling
and innovative clinical trials exploring novel drug combinations to
improve patient outcomes. ESCC, esophageal squamous cell carcinoma;
AD, antibody-drug conjugate; ICIs, immune checkpoint inhibitors;
CAR-T cell, chimeric antigen receptor T cell. Created by
Figdraw.
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Copy and paste a formatted citation
Spandidos Publications style
Li Y, Li J, Mo W and Xu X: Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review). Oncol Rep 54: 120, 2025.
APA
Li, Y., Li, J., Mo, W., & Xu, X. (2025). Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review). Oncology Reports, 54, 120. https://doi.org/10.3892/or.2025.8953
MLA
Li, Y., Li, J., Mo, W., Xu, X."Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review)". Oncology Reports 54.4 (2025): 120.
Chicago
Li, Y., Li, J., Mo, W., Xu, X."Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review)". Oncology Reports 54, no. 4 (2025): 120. https://doi.org/10.3892/or.2025.8953
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Li J, Mo W and Xu X: Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review). Oncol Rep 54: 120, 2025.
APA
Li, Y., Li, J., Mo, W., & Xu, X. (2025). Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review). Oncology Reports, 54, 120. https://doi.org/10.3892/or.2025.8953
MLA
Li, Y., Li, J., Mo, W., Xu, X."Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review)". Oncology Reports 54.4 (2025): 120.
Chicago
Li, Y., Li, J., Mo, W., Xu, X."Changing landscape of advanced esophageal squamous cell carcinoma: Breakthroughs in systemic therapies (Review)". Oncology Reports 54, no. 4 (2025): 120. https://doi.org/10.3892/or.2025.8953
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