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Cancers
Special Issues
Personalized Therapies in Oesophageal Cancer
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Personalized Therapies in Oesophageal Cancer

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

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 11240

Special Issue Editors

Prof. Dr. Tim Underwood

E-Mail Website
Guest Editor
School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK
Interests: oesophageal cancer; tumour microenvironment; tumour ecosystems; predicting response to treatment; machine learning and AI in surgery
Dr. Zoe Walters

E-Mail Website
Guest Editor
School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK
Interests: oesophageal cancer; target identification and validation; model systems; predicting response to treatment; biomarker discovery; drug discovery; personalized medicine

Special Issue Information

Dear Colleagues, 

Despite advances in surgery, oncology and immunotherapy, most oesophageal cancer patients die from their disease and most fail to respond to treatment. The development of precision treatments has been disappointing, hampered by a scarcity of recurrent, targetable driver events and cellular and genetic heterogeneity within and between primary tumors and metastases. A bespoke multi-therapeutic approach may be necessary to deliver a clinically meaningful response. 

Large-scale genome sequencing studies have begun to define the landscape of mutations in both major histological subtypes of the disease: squamous cell cancer and adenocarcinoma. Unfortunately, they are yet to result in real advances in treatment and survival.

This Special Issue of Cancers will cover original research and comprehensive reviews on novel and strategic approaches to the management and treatment of oesophageal cancer. Topics of interest include, but are not limited to, investigational therapies involving surgery, chemo/radiotherapy or immunotherapy-based targeted agents in pre-clinical or clinical settings; molecular mechanisms of treatment response or design strategies; and the use of robust clinical or molecular-based prognostic or predictive biomarkers. We encourage the submission of research utilising machine-learning and AI based strategies. We aim to provide an update on the current status and future directions of this exciting field of research that aims to improve oesophageal cancer patient outcomes.

Prof. Dr. Tim Underwood
Dr. Zoe Walters
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 short 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

  • oesophageal cancer
  • treatment response
  • surgery
  • prognosis
  • machine learning
  • AI
  • targeted therapies

Published Papers (5 papers)

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Research

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18 pages, 3186 KiB  
Article
Identification of Src as a Therapeutic Target in Oesophageal Adenocarcinoma through Functional Genomic and High-Throughput Drug Screening Approaches
by Niamh H. McCabe, Leanne Stevenson, Enya Scanlon, Rosalie Douglas, Susanna Kennedy, Oliver Keminer, Björn Windshügel, Daniela Zisterer, Richard D. Kennedy, Jaine K. Blayney and Richard C. Turkington
Cancers 2022, 14(15), 3726; https://doi.org/10.3390/cancers14153726 - 30 Jul 2022
Cited by 1 | Viewed by 1665
Abstract
Drug resistance limits the effectiveness of oesophageal adenocarcinoma (OAC) chemotherapies, leading to a poor prognosis for this disease. Elucidation of the underlying resistance mechanisms is key to enabling the identification of more effective treatments. This study, therefore, aims to identify novel therapeutic and/or [...] Read more.
Drug resistance limits the effectiveness of oesophageal adenocarcinoma (OAC) chemotherapies, leading to a poor prognosis for this disease. Elucidation of the underlying resistance mechanisms is key to enabling the identification of more effective treatments. This study, therefore, aims to identify novel therapeutic and/or chemotherapy sensitising drug targets in OAC. Transcriptional data from a cohort of 273 pre-treatment OAC biopsies, from patients who received neoadjuvant chemotherapy followed by surgical resection, were analysed using gene set enrichment analysis (GSEA) to determine differential gene expression between responding and non-responding OAC tumours. From this, 80 genes were selected for high-throughput siRNA screening in OAC cell lines with or without standard chemotherapy treatment. In parallel, cell viability assays were performed using a panel of FDA-approved drugs and combination index (CI) values were calculated to evaluate drug synergy with standard chemotherapy. Mechanisms of synergy were investigated using western blot, propidium iodide flow cytometry, and proliferation assays. Taken together, the screens identified that targeting Src, using either siRNA or the small molecule inhibitor dasatinib, enhanced the efficacy of chemotherapy in OAC cells. Further in vitro functional analysis confirmed Src inhibition to be synergistic with standard OAC chemotherapies, 5-fluorouracil (5-FU), and cisplatin (CDDP). In conclusion, a compound screen together with a functional genomic approach identified Src as a potential chemosensitising target in OAC, which could be assessed in a clinical study for poor prognosis OAC patients. Full article
(This article belongs to the Special Issue Personalized Therapies in Oesophageal Cancer)
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12 pages, 793 KiB  
Article
cT1N0M0 Esophageal Squamous Cell Carcinoma Invades the Muscularis Mucosa or Submucosa: Comparison of the Results of Endoscopic Submucosal Dissection and Esophagectomy
by Ching-Ya Wang, Bo-Huan Chen, Cheng-Han Lee, Puo-Hsien Le, Yung-Kuan Tsou and Cheng-Hui Lin
Cancers 2022, 14(2), 424; https://doi.org/10.3390/cancers14020424 - 15 Jan 2022
Cited by 6 | Viewed by 1704
Abstract
Background: Endoscopic submucosal dissection (ESD) combined with selective adjuvant chemoradiotherapy may be a new treatment option for cT1N0M0 esophageal squamous cell carcinoma (ESCC) invading muscularis mucosa or submucosa (pT1a-M3/pT1b). We aim to report the effectiveness of this treatment by comparing the results of [...] Read more.
Background: Endoscopic submucosal dissection (ESD) combined with selective adjuvant chemoradiotherapy may be a new treatment option for cT1N0M0 esophageal squamous cell carcinoma (ESCC) invading muscularis mucosa or submucosa (pT1a-M3/pT1b). We aim to report the effectiveness of this treatment by comparing the results of esophagectomy. Methods: This retrospective single-center study included 72 patients with pT1a-M3/pT1b ESCC who received ESD combined with selective adjuvant chemoradiotherapy (n = 40) and esophagectomy (n = 32). The main outcome comparison was overall survival (OS). The secondary outcomes were treatment-related events, including operation time, complication rate, and length of hospital stay. Disease-specific survival (DSS) and progression-free survival (PFS) were also evaluated. Results: There were no significant differences in the rates of OS, DSS, and PFS between the two groups (median follow-up time: 49.2 months vs. 50.9 months); these were also the same in the subgroup analysis of pT1b ESCC patients. In the ESD group, the procedure time, overall complication rates, and length of hospital stay were significantly reduced. However, the metachronous recurrence rate was significantly higher. In a multivariate analysis, tumor depth and R0 resection were the independent factors associated with OS. Conclusions: ESD combined with selective adjuvant chemoradiotherapy can be an alternative treatment to esophagectomy for cT1N0M0 ESCC invading muscularis mucosa or submucosa. Full article
(This article belongs to the Special Issue Personalized Therapies in Oesophageal Cancer)
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Review

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18 pages, 658 KiB  
Review
Current and Future Immunotherapy-Based Treatments for Oesophageal Cancers
by Natalie To, Richard P. T. Evans, Hayden Pearce, Sivesh K. Kamarajah, Paul Moss and Ewen A. Griffiths
Cancers 2022, 14(13), 3104; https://doi.org/10.3390/cancers14133104 - 24 Jun 2022
Viewed by 1955
Abstract
Oesophageal cancer is a disease that causes significant morbidity and mortality worldwide, and the prognosis of this condition has hardly improved in the past few years. Standard treatment includes a combination of chemotherapy, radiotherapy and surgery; however, only a proportion of patients go [...] Read more.
Oesophageal cancer is a disease that causes significant morbidity and mortality worldwide, and the prognosis of this condition has hardly improved in the past few years. Standard treatment includes a combination of chemotherapy, radiotherapy and surgery; however, only a proportion of patients go on to treatment intended to cure the disease due to the late presentation of this disease. New treatment options are of utmost importance, and immunotherapy is a new option that has the potential to transform the landscape of this disease. This treatment is developed to act on the changes within the immune system caused by cancer, including checkpoint inhibitors, which have recently shown great promise in the treatment of this disease and have recently been included in the adjuvant treatment of oesophageal cancer in many countries worldwide. This review will outline the mechanisms by which cancer evades the immune system in those diagnosed with oesophageal cancer and will summarize current and ongoing trials that focus on the use of our own immune system to combat disease. Full article
(This article belongs to the Special Issue Personalized Therapies in Oesophageal Cancer)
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22 pages, 2238 KiB  
Review
The Use of miRNAs in Predicting Response to Neoadjuvant Therapy in Oesophageal Cancer
by Cameron C. J. Lang, Megan Lloyd, Said Alyacoubi, Saqib Rahman, Oliver Pickering, Tim Underwood and Stella P. Breininger
Cancers 2022, 14(5), 1171; https://doi.org/10.3390/cancers14051171 - 24 Feb 2022
Cited by 3 | Viewed by 2463
Abstract
Oesophageal cancer (OC) is the ninth most common cancer worldwide. Patients receive neoadjuvant therapy (NAT) as standard of care, but less than 20% of patients with oesophageal adenocarcinoma (OAC) or a third of oesophageal squamous cell carcinoma (OSCC) patients, obtain a clinically meaningful [...] Read more.
Oesophageal cancer (OC) is the ninth most common cancer worldwide. Patients receive neoadjuvant therapy (NAT) as standard of care, but less than 20% of patients with oesophageal adenocarcinoma (OAC) or a third of oesophageal squamous cell carcinoma (OSCC) patients, obtain a clinically meaningful response. Developing a method of determining a patient’s response to NAT before treatment will allow rational treatment decisions to be made, thus improving patient outcome and quality of life. (1) Background: To determine the use and accuracy of microRNAs as biomarkers of response to NAT in patients with OAC or OSCC. (2) Methods: MEDLINE, EMBASE, Web of Science and the Cochrane library were searched to identify studies investigating microRNAs in treatment naïve biopsies to predict response to NAT in OC patients. (3) Results: A panel of 20 microRNAs were identified as predictors of good or poor response to NAT, from 15 studies. Specifically, miR-99b, miR-451 and miR-505 showed the strongest ability to predict response in OAC patients along with miR-193b in OSCC patients. (4) Conclusions: MicroRNAs are valuable biomarkers of response to NAT in OC. Research is needed to understand the effects different types of chemotherapy and chemoradiotherapy have on the predictive value of microRNAs; studies also require greater standardization in how response is defined. Full article
(This article belongs to the Special Issue Personalized Therapies in Oesophageal Cancer)
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37 pages, 684 KiB  
Review
Predicting Response to Neoadjuvant Therapy in Oesophageal Adenocarcinoma
by William Jiang, Jelske M. de Jong, Richard van Hillegersberg and Matthew Read
Cancers 2022, 14(4), 996; https://doi.org/10.3390/cancers14040996 - 16 Feb 2022
Cited by 4 | Viewed by 2606
Abstract
(1) Background: Oesophageal cancers are often late-presenting and have a poor 5-year survival rate. The standard treatment of oesophageal adenocarcinomas involves neoadjuvant chemotherapy with or without radiotherapy followed by surgery. However, less than one third of patients respond to neoadjuvant therapy, thereby unnecessarily [...] Read more.
(1) Background: Oesophageal cancers are often late-presenting and have a poor 5-year survival rate. The standard treatment of oesophageal adenocarcinomas involves neoadjuvant chemotherapy with or without radiotherapy followed by surgery. However, less than one third of patients respond to neoadjuvant therapy, thereby unnecessarily exposing patients to toxicity and deconditioning. Hence, there is an urgent need for biomarkers to predict response to neoadjuvant therapy. This review explores the current biomarker landscape. (2) Methods: MEDLINE, EMBASE and ClinicalTrial databases were searched with key words relating to “predictive biomarker”, “neoadjuvant therapy” and “oesophageal adenocarcinoma” and screened as per the inclusion and exclusion criteria. All peer-reviewed full-text articles and conference abstracts were included. (3) Results: The search yielded 548 results of which 71 full-texts, conference abstracts and clinical trials were eligible for review. A total of 242 duplicates were removed, 191 articles were screened out, and 44 articles were excluded. (4) Discussion: Biomarkers were discussed in seven categories including imaging, epigenetic, genetic, protein, immunologic, blood and serum-based with remaining studies grouped in a miscellaneous category. (5) Conclusion: Although promising markers and novel methods have emerged, current biomarkers lack sufficient evidence to support clinical application. Novel approaches have been recommended to assess predictive potential more efficiently. Full article
(This article belongs to the Special Issue Personalized Therapies in Oesophageal Cancer)
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