Advances in Esophageal Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 15 August 2025 | Viewed by 936

Special Issue Editor


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Guest Editor
Department of Upper GI Surgery, Royal Marsden Hospital, London, UK
Interests: oesophageal cancer; gastric cancer; gastrointestinal stromal tumours; benign upper gastrointestinal surgery; upper gastrointestinal endoscopy
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Special Issue Information

Dear Colleagues,

Esophageal cancer is a disease with significant unmet clinical needs. Challenges in early diagnosis and ineffective systemic and local therapies contribute to why five-year survival is just 15%. Despite treatment with a potentially curative intent, nearly 40% of patients who achieve a complete pathological response recur within two years of completing treatment. Recurrent disease can present insidiously, and subsequent survival despite systemic and local therapy is often poor.

Detecting recurrent esophageal cancer remains a challenge. Although significant research has been undertaken on the role of serum biomarkers including circulating tumor DNA in disease surveillance and in monitoring response to therapy, there is a lack of assays with sensitivity and specificity adequate for use in the current mainstream practice. Early detection of recurrence may enable patients to undergo targeted therapy, thereby improving long-term survival.

This Special Issue focuses on the latest developments in monitoring efficacy of treatment, disease surveillance, and early detection of recurrence to help improve long-term survival.

Dr. Sacheen Kumar
Guest Editor

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Keywords

  • esophageal adenocarcinoma
  • esophageal squamous cell carcinoma
  • long-term survival
  • biomarkers
  • disease surveillance
  • treatment response

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Published Papers (2 papers)

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Research

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25 pages, 3998 KiB  
Article
CRISPR/Cas9 Screening Highlights PFKFB3 Gene as a Major Contributor to 5-Fluorouracil Resistance in Esophageal Cancer
by Feng Xue, Hai Yang, Pengyan Xu, Shuman Zhang, Nathalie Britzen-Laurent, Li-Li Bao, Robert Grützmann, Christian Krautz and Christian Pilarsky
Cancers 2025, 17(10), 1637; https://doi.org/10.3390/cancers17101637 - 12 May 2025
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Abstract
Background: Esophageal cancer (EC) is the eighth most common cancer and the sixth most common cause of death worldwide. Esophageal squamous cell carcinoma (ESCC) comprises the majority of esophageal cancers globally, and 5-Fluorouraci (5-FU) is one of the commonly used chemotherapeutics for this [...] Read more.
Background: Esophageal cancer (EC) is the eighth most common cancer and the sixth most common cause of death worldwide. Esophageal squamous cell carcinoma (ESCC) comprises the majority of esophageal cancers globally, and 5-Fluorouraci (5-FU) is one of the commonly used chemotherapeutics for this type of cancer. Chemoresistance to drugs is a main obstacle in the successful treatment of this malignancy. Methods: In this study, we used the CRISPR/Cas9 screening method to determine the target gene related to 5-FU drug resistance in esophageal cancer. Results: Our research findings indicate that the loss of PFKFB3 can increase the resistance of different human esophageal squamous cell carcinoma cell lines to 5-FU through various pathways. Specifically, in KYSE-70 cells, loss of PFKFB3 can induce epithelial–mesenchymal transition (EMT) and prolong the S phase of the cell cycle, allowing cancer cells to evade the effects of 5-FU and develop resistance. In the KYSE-270 and KYSE-150 cell lines, loss of PFKFB3 can upregulate the expression of Slug and Mcl-1, indirectly regulate Chk1 and promote its autophosphorylation, which in turn inhibits apoptosis, thus counteracting the effects of 5-FU. Conclusions: Our research not only enriches our understanding of the biological characteristics of different ESCC cell lines but also provides new clinical insights for future personalized treatments. Assessing the status of PFKFB3 can help predict resistance to 5-FU in ESCC patients with different genetic backgrounds, allowing for more precise treatment planning. This personalized approach has the potential to improve treatment efficacy, reduce unnecessary drug use and side effects, and ultimately improve patient survival rates and quality of life. Full article
(This article belongs to the Special Issue Advances in Esophageal Cancer)
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Review

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34 pages, 4621 KiB  
Review
Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies
by Yahui Li, Zachary Ladd, Zhaohui Xiong, Candice Bui-Linh, Chorlada Paiboonrungruang, Boopathi Subramaniyan, Huan Li, Haining Wang, Curt Balch, David D. Shersher, Francis Spitz and Xiaoxin Chen
Cancers 2025, 17(11), 1853; https://doi.org/10.3390/cancers17111853 - 31 May 2025
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Abstract
The lethality of esophageal squamous cell carcinoma (ESCC), and other epithelial cancers, is primarily due to its aggressive nature and frequent lymphatic metastasis, both of which impact prognosis. In this review, we explore the underlying molecular mechanisms of ESCC lymphatic metastasis, specifically, the [...] Read more.
The lethality of esophageal squamous cell carcinoma (ESCC), and other epithelial cancers, is primarily due to its aggressive nature and frequent lymphatic metastasis, both of which impact prognosis. In this review, we explore the underlying molecular mechanisms of ESCC lymphatic metastasis, specifically, the functional role of NRF2 and therapeutic strategies. Current data suggest that NRF2 hyperactivation (NRF2high) may promote lymphatic metastasis of ESCC by affecting the extracellular matrix (ECM), epithelial–mesenchymal transition (EMT), lymphangiogenesis, immune evasion, metabolic programming, and Hippo signaling. We also update the latest developments in NRF2 inhibitors, their mechanisms of action, screening strategies, and approaches for evaluating compound efficacy. Finally, we highlight the utility of animal models for mechanistic studies and therapeutic development. We believe elucidation of the functional role of NRF2 in ESCC lymphatic metastasis and developing proper NRF2 inhibitors will greatly improve the clinical prognosis of ESCC in human patients. Full article
(This article belongs to the Special Issue Advances in Esophageal Cancer)
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