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Cancers
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Emerging Therapeutic Approaches to Esophageal Cancer
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Emerging Therapeutic Approaches to Esophageal Cancer

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

Deadline for manuscript submissions: closed (30 August 2023) | Viewed by 7693

Special Issue Editors

Dr. Pornima Phatak

E-Mail Website
Guest Editor
1. Birmingham Veterans Affairs Health Care System, Birmingham, AL 35233, USA
2. Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA
Interests: microRNA; migration; invasion; apoptosis; PAK4; RAB14
Special Issues, Collections and Topics in MDPI journals
Dr. James M. Donahue

E-Mail Website
Guest Editor
1. Birmingham Veterans Affairs Health Care System, Birmingham, AL 35233, USA
2. Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA
Interests: esophageal cancer; CUG-BP1; survivin; post translational regulation; cell proliferation
Special Issues, Collections and Topics in MDPI journals
Dr. Kaushal Asrani

E-Mail Website
Guest Editor
Johns Hopkins School of Medicine, Baltimore, MD, USA
Interests: mTORC1; TSC; autophagy; lysosomes; TFEB; TFE3; renal tumors

Special Issue Information

Dear Colleagues, 

The incidence of esophageal cancer is continuously increasing and is one of the least studied and deadliest malignancies, worldwide. Due to a lack of early diagnosis, it often presents at an advanced stage. Currently, standard treatment for locally advanced esophageal cancer involves chemotherapy and/or radiation therapy prior to surgery. Despite this trimodality approach, survival remains very poor with a five-year survival rate of 20%. Thus, alternative therapeutic strategies that serve adjunctive roles to surgery are required to improve survival in esophageal cancer patients.

Dr. Pornima Phatak
Dr. James M. Donahue
Dr. Kaushal Asrani
Guest Editors

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.

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Published Papers (4 papers)

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Research

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20 pages, 6723 KiB  
Article
MiR-199a-5p Decreases Esophageal Cancer Cell Proliferation Partially through Repression of Jun-B
by Pornima Phatak, Mohan E. Tulapurkar, Whitney M. Burrows and James M. Donahue
Cancers 2023, 15(19), 4811; https://doi.org/10.3390/cancers15194811 - 30 Sep 2023
Cited by 3 | Viewed by 1423
Abstract
MicroRNA (miR)-199a-5p has been shown to function as a tumor suppressor in some malignancies but its role in esophageal cancer is poorly understood. To further explore its role in esophageal cancer, we sought to investigate the interaction between miR-199a-5p and Jun-B, an important [...] Read more.
MicroRNA (miR)-199a-5p has been shown to function as a tumor suppressor in some malignancies but its role in esophageal cancer is poorly understood. To further explore its role in esophageal cancer, we sought to investigate the interaction between miR-199a-5p and Jun-B, an important component of the AP1 transcription factor, which contains a potential binding site for miR-199a-5p in its mRNA. We found that levels of miR-199a-5p are reduced in both human esophageal cancer specimens and in multiple esophageal cancer cell lines compared to esophageal epithelial cells. Jun-B expression is correspondingly elevated in these tumor specimens and in several cell lines compared to esophageal epithelial cells. Jun-B mRNA expression and stability, as well as protein expression, are markedly decreased following miR-199a-5p overexpression. A direct interaction between miR-199a-5p and Jun-B mRNA was confirmed by a biotinylated RNA-pull down assay and luciferase reporter constructs. Either forced expression of miR-199a-5p or Jun-B silencing led to a significant decrease in cellular proliferation as well as in AP-1 promoter activity. Our results provide evidence that miR-199a-5p functions as a tumor suppressor in esophageal cancer cells by regulating cellular proliferation, partially through repression of Jun B. Full article
(This article belongs to the Special Issue Emerging Therapeutic Approaches to Esophageal Cancer)
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18 pages, 5743 KiB  
Article
Chemoradiotherapy Combined with Brachytherapy for the Definitive Treatment of Esophageal Carcinoma
by Julian Mangesius, Katharina Hörmandinger, Robert Jäger, Sergej Skvortsov, Marlen Plankensteiner, Martin Maffei, Thomas Seppi, Daniel Dejaco, Matthias Santer, Manuel Sarcletti and Ute Ganswindt
Cancers 2023, 15(14), 3594; https://doi.org/10.3390/cancers15143594 - 12 Jul 2023
Cited by 2 | Viewed by 1978
Abstract
This study aims to investigate the effect of dose escalation with brachytherapy (BT) as an addition to definitive chemoradiotherapy (CRT) on local control and survival in esophageal cancer. From 2001 to 2020, 183 patients with locally limited or locally advanced esophageal cancer received [...] Read more.
This study aims to investigate the effect of dose escalation with brachytherapy (BT) as an addition to definitive chemoradiotherapy (CRT) on local control and survival in esophageal cancer. From 2001 to 2020, 183 patients with locally limited or locally advanced esophageal cancer received definitive CRT with or without brachytherapy in a two-center study. External-beam radiotherapy was delivered at 50.4 Gy in 1.8 Gy daily fractions, followed by a sequential boost to the primary tumor of 9 Gy in 1.8 Gy daily fractions if indicated. Intraluminal high dose rate (HDR) Ir-192 brachytherapy was performed on 71 patients at 10 Gy in two fractions, with one fraction per week. The combined systemic therapy schedules used included 5-fluorouracil/cisplatin or 5-fluorouracil alone. Cisplatin was not administered in patients receiving brachytherapy. The median local progression-free survival was significantly extended in the BT group (18.7 vs. 6.0 months; p < 0.0001), and the median local control was also significantly prolonged (30.5 vs. 11.3 months, p = 0.008). Overall survival (OS) significantly increased in the BT group (median OS 22.7 vs. 9.1 months, p < 0.0001). No significant difference in the overall rate of acute toxicities was observed; however, the rate of acute esophagitis was significantly higher in the BT group (94.4% vs. 81.2%). Likewise, the overall rate of late toxicities (43.7% vs. 18.8%) was significantly higher in the BT group, including the rate of esophageal stenosis (22.5% vs. 9.8%). There was no difference in the occurrence of life-threatening or lethal late toxicities (grades 4 and 5). Brachytherapy, after chemoradiation with single-agent 5-FU, represents a safe and effective alternative for dose escalation in the definitive treatment of esophageal cancer. Full article
(This article belongs to the Special Issue Emerging Therapeutic Approaches to Esophageal Cancer)
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12 pages, 1732 KiB  
Article
Endoscopic Resection of Residual or Recurrent Lesions after Circumferential Radiofrequency Ablation for Flat Superficial Esophageal Squamous Cell Neoplasias
by Yung-Kuan Tsou, Chi-Ju Yeh, Puo-Hsien Le, Bo-Huan Chen and Cheng-Hui Lin
Cancers 2023, 15(14), 3558; https://doi.org/10.3390/cancers15143558 - 10 Jul 2023
Cited by 1 | Viewed by 1351
Abstract
The optimal treatment of residual/recurrent superficial esophageal squamous cell neoplasias (SESCNs) after circumferential radiofrequency (RFA) remains unclear. We aimed to report the efficacy and safety of endoscopic resection (ER) of residual/recurrent SESCNs after RFA. Patients who underwent circumferential RFA with residual/recurrent SESCNs and [...] Read more.
The optimal treatment of residual/recurrent superficial esophageal squamous cell neoplasias (SESCNs) after circumferential radiofrequency (RFA) remains unclear. We aimed to report the efficacy and safety of endoscopic resection (ER) of residual/recurrent SESCNs after RFA. Patients who underwent circumferential RFA with residual/recurrent SESCNs and were treated with ER were retrospectively collected. SESCN patients treated with primary endoscopic submucosal dissection (ESD) served as the control group. Eleven patients who underwent RFA had a total of 17 residual (n = 8) or recurrent (n = 9) SESCNs and were treated for ER. EMR failed to remove one residual SESCN. Of the 16 resected specimens, 10 were high-grade intraepithelial neoplasia (HGIN) and six were cancer. Eight cases had neoplasia extending to esophageal ducts/submucosal glands (SMGs). The pathological results may imply three possible routes in which residual/recurrent SESCNs occurred: HGIN without ductal/SMG involvement (37.5%), HGIN with ductal/SMG involvement (25.0%), and SCC with muscularis mucosae or deeper involvement (37.5%). Compared with the control group, the study group had similar procedural speed, en bloc resection rate, R0 resection rate, and complication rate. In conclusion, the safety and efficacy of post-RFA ESD were similar to those of primary ESD. ESD should be the treatment of choice for residual/recurrent SESCNs after initial RFA. Full article
(This article belongs to the Special Issue Emerging Therapeutic Approaches to Esophageal Cancer)
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Review

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15 pages, 691 KiB  
Review
The Local Microbiome in Esophageal Cancer and Treatment Response: A Review of Emerging Data and Future Directions
by Abhishek Pandey, Christopher H. Lieu and Sunnie S. Kim
Cancers 2023, 15(14), 3562; https://doi.org/10.3390/cancers15143562 - 10 Jul 2023
Cited by 5 | Viewed by 2329
Abstract
The incidence of esophageal cancer is increasing worldwide, with established risk factors explaining only a small fraction of cases. Currently, there are no established screening protocols in most countries, and treatment options are limited. The human microbiome has been implicated in carcinogenesis and [...] Read more.
The incidence of esophageal cancer is increasing worldwide, with established risk factors explaining only a small fraction of cases. Currently, there are no established screening protocols in most countries, and treatment options are limited. The human microbiome has been implicated in carcinogenesis and the cancer treatment response. The advent of nucleic acid sequencing technologies has enabled more comprehensive, culture-independent bacterial identification. Across several tumor types, studies of tissue-specific microbiomes have shown associations between the overall microbiome composition, the relative abundance of specific bacteria, and tumorigenesis. Furthermore, in the era of cancer immunotherapy, several studies have demonstrated that the microbiome and specific bacteria may modify treatment responses and the risk of immune-related adverse events. Design: peer-reviewed, published studies describing the role of local, gastrointestinal-specific microbiota or the role of the gut microbiome in treatment responses were reviewed. PubMed was searched from 1 September 2022 to 1 November 2022, using the following terms in combination: “microbiome”, “tumor microbiome”, “esophageal cancer”, “cancer”, “cancer treatment”, and “immunotherapy”. Original research articles were considered, and other reviews or editorials were discarded. In total, approximately 250 articles were considered. Results: over 70 studies describing microbiome research in either gastrointestinal carcinogenesis or the systemic treatment response were identified and reviewed. Conclusions: a growing body of evidence supports the role of the esophageal microbiome in both esophageal tumorigenesis and the immune checkpoint inhibitor response. More well-designed, comprehensive studies are required to collect the appropriate clinical, microbial, and immunophenotype data that are needed to clarify the precise role of the microbiome in esophageal carcinogenesis and treatment. Full article
(This article belongs to the Special Issue Emerging Therapeutic Approaches to Esophageal Cancer)
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