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Advances in Esophageal Cancer
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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 February 2026 | Viewed by 5589

Special Issue Editor

Dr. Sacheen Kumar

E-Mail Website
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
Special Issues, Collections and Topics in MDPI journals

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

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Published Papers (4 papers)

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Research

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13 pages, 874 KB  
Article
Real-World Effectiveness of Cisplatin, 5-Fluorouracil, and Pembrolizumab Combination Therapy for Unresectable or Recurrent Esophageal Cancer
by Yu Ueta, Masanobu Nakajima, Masaki Yoshimatsu, Takahiro Ochiai, Shuhei Takise, Junki Fujita, Masatoshi Nakagawa, Shinji Morita and Kazuyuki Kojima
Cancers 2025, 17(19), 3202; https://doi.org/10.3390/cancers17193202 - 1 Oct 2025
Viewed by 471
Abstract
Background: Immune checkpoint inhibitors (ICIs) such as pembrolizumab (Pem) have demonstrated clinical benefits in esophageal cancer. Cisplatin, 5-fluorouracil, and Pem combination (CF plus Pem) has emerged as a promising first-line regimen. However, dose reduction of cytotoxic agents is necessary in real-world practice in [...] Read more.
Background: Immune checkpoint inhibitors (ICIs) such as pembrolizumab (Pem) have demonstrated clinical benefits in esophageal cancer. Cisplatin, 5-fluorouracil, and Pem combination (CF plus Pem) has emerged as a promising first-line regimen. However, dose reduction of cytotoxic agents is necessary in real-world practice in patients with advanced age and/or renal dysfunction. This study aimed to evaluate the real-world effectiveness and safety of CF plus Pem therapy and assess survival outcomes based on the initial dose intensity. Methods: We retrospectively analyzed patients with unresectable or recurrent esophageal cancer who received CF plus Pem between February 2022 and February 2025. Clinical data, including patient characteristics, treatment details, tumor response, adverse events, and survival outcomes, were collected and analyzed. Results: We included 54 patients (median age, 72.5 years; 74.1% male). The initial CF dose was reduced in 55.6% of the patients. The overall response and disease control rates were 55.6% and 81.5%, respectively. The median overall survival (OS) and progression-free survival (PFS) were 18.6 and 6.5 months, respectively, with no significant differences observed among groups based on dose reduction, age, or change in treatment interval. Grade ≥ 3 adverse events occurred in 16.7% of patients, with fewer events and higher treatment continuity in the dose-reduction group. Conclusions: Thus, CF plus Pem therapy is effective and tolerable in real-world settings. Initial dose reduction does not compromise survival and supports individualized dosing strategies for esophageal cancer treatment. Full article
(This article belongs to the Special Issue Advances in Esophageal Cancer)
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25 pages, 3998 KB  
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
Viewed by 1393
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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14 pages, 403 KB  
Review
Organ Preservation in Esophageal Cancer: Current Strategies, Challenges, and Future Directions
by Wenyi Liu, Baihua Zhang, Chunguang Wang, Xin Yu, Longde Du, Zhentao Yu and Mingqiang Kang
Cancers 2025, 17(21), 3559; https://doi.org/10.3390/cancers17213559 - 3 Nov 2025
Abstract
Esophageal cancer (EC) continues to pose a major global health burden, ranking as the ninth most common malignancy and sixth leading cause of cancer mortality, with over 600,000 new cases and 500,000 deaths annually as of 2025. While esophagectomy has long been the [...] Read more.
Esophageal cancer (EC) continues to pose a major global health burden, ranking as the ninth most common malignancy and sixth leading cause of cancer mortality, with over 600,000 new cases and 500,000 deaths annually as of 2025. While esophagectomy has long been the standard for curative intent in resectable disease, organ preservation strategies have advanced significantly, offering viable alternatives for patients with locally advanced esophageal squamous cell carcinoma (ESCC) or those unsuitable for surgery due to comorbidities. These approaches encompass definitive chemoradiotherapy (dCRT), neoadjuvant chemoradiotherapy (nCRT) followed by active surveillance (“watch-and-wait”), and innovative integrations of immunotherapy and targeted therapies. This narrative review synthesizes evidence from recent clinical trials, systematic reviews, and international guidelines up to 2025, demonstrating that organ-sparing protocols can achieve comparable overall survival (OS) rates—often exceeding 50% at 5 years in selected cohorts-while substantially enhancing quality of life (QoL) by preserving esophageal function. For instance, the SANO trial (2025) confirmed non-inferiority of active surveillance post-nCRT, with 2-year OS of 74% versus 71% for standard surgery. Key challenges include imprecise response assessment, locoregional recurrences (20–30%), and treatment-related toxicities such as esophageal strictures. Emerging trials like ESOSTRATE and PALACE3 are evaluating immunotherapy-enhanced regimens, potentially expanding organ preservation to esophageal adenocarcinoma (EAC). With genomic biomarkers and novel modalities like proton therapy, personalized organ preservation promises to broaden applicability, reduce morbidity, and improve outcomes across histological subtypes. Additionally, recent studies emphasize the role of liquid biopsies, such as circulating tumor DNA (ctDNA), in monitoring treatment response and guiding surveillance, potentially reducing the need for invasive procedures and improving detection of minimal residual disease. The aim of this review is not only to summarize recent trials but to synthesize them into an operational framework that clinicians and researchers can apply: a decision algorithm for selecting organ preservation candidates. This is the novel element that distinguishes this work from prior narrative reviews. Full article
(This article belongs to the Special Issue Advances in Esophageal Cancer)
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34 pages, 4621 KB  
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
Cited by 3 | Viewed by 3064
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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