The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma
Gastroesophageal junction adenocarcinomas (GEJA) have dramatically increased in incidence in the western world since the mid-20th century. Their prognosis is poor, and conventional anti-cancer therapies do not significantly improve survival outcomes. These tumours are comprised of a heterogenous pop...
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| Format: | Article |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.600373/full |
| _version_ | 1819275445909061632 |
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| author | Kate Dinneen Kate Dinneen Anne-Marie Baird Ciara Ryan Orla Sheils |
| author_facet | Kate Dinneen Kate Dinneen Anne-Marie Baird Ciara Ryan Orla Sheils |
| author_sort | Kate Dinneen |
| collection | DOAJ |
| description | Gastroesophageal junction adenocarcinomas (GEJA) have dramatically increased in incidence in the western world since the mid-20th century. Their prognosis is poor, and conventional anti-cancer therapies do not significantly improve survival outcomes. These tumours are comprised of a heterogenous population of both cancer stem cells (CSC) and non-CSCs, with the former playing a crucial role in tumorigenesis, metastasis and importantly drug resistance. Due to the ability of CSCs to self-replicate indefinitely, their resistance to anti-cancer therapies poses a significant barrier to effective treatment of GEJA. Ongoing drug development programmes aim to target and eradicate CSCs, however their characterisation and thus identification is difficult. CSC regulation is complex, involving an array of signalling pathways, which are in turn influenced by a number of entities including epithelial mesenchymal transition (EMT), microRNAs (miRNAs), the tumour microenvironment and epigenetic modifications. Identification of CSCs commonly relies on the expression of specific cell surface markers, yet these markers vary between different malignancies and indeed are often co-expressed in non-neoplastic tissues. Development of targeted drug therapies against CSCs thus requires an understanding of disease-specific CSC markers and regulatory mechanisms. This review details the current knowledge regarding CSCs in GEJA, with particular emphasis on their role in drug resistance. |
| first_indexed | 2024-12-23T23:24:27Z |
| format | Article |
| id | doaj.art-372179c9fb554cb4b49337525297ffbf |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-23T23:24:27Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-372179c9fb554cb4b49337525297ffbf2022-12-21T17:26:16ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-02-01810.3389/fmolb.2021.600373600373The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction AdenocarcinomaKate Dinneen0Kate Dinneen1Anne-Marie Baird2Ciara Ryan3Orla Sheils4School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, IrelandDepartment of Histopathology, St. James’s Hospital, Dublin, IrelandSchool of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, IrelandDepartment of Histopathology, St. James’s Hospital, Dublin, IrelandSchool of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, IrelandGastroesophageal junction adenocarcinomas (GEJA) have dramatically increased in incidence in the western world since the mid-20th century. Their prognosis is poor, and conventional anti-cancer therapies do not significantly improve survival outcomes. These tumours are comprised of a heterogenous population of both cancer stem cells (CSC) and non-CSCs, with the former playing a crucial role in tumorigenesis, metastasis and importantly drug resistance. Due to the ability of CSCs to self-replicate indefinitely, their resistance to anti-cancer therapies poses a significant barrier to effective treatment of GEJA. Ongoing drug development programmes aim to target and eradicate CSCs, however their characterisation and thus identification is difficult. CSC regulation is complex, involving an array of signalling pathways, which are in turn influenced by a number of entities including epithelial mesenchymal transition (EMT), microRNAs (miRNAs), the tumour microenvironment and epigenetic modifications. Identification of CSCs commonly relies on the expression of specific cell surface markers, yet these markers vary between different malignancies and indeed are often co-expressed in non-neoplastic tissues. Development of targeted drug therapies against CSCs thus requires an understanding of disease-specific CSC markers and regulatory mechanisms. This review details the current knowledge regarding CSCs in GEJA, with particular emphasis on their role in drug resistance.https://www.frontiersin.org/articles/10.3389/fmolb.2021.600373/fullcancer stem cellsdrug resistancegastroesophageal junction adenocarcinomaepithelial mesenchymal transitionmicroRNA |
| spellingShingle | Kate Dinneen Kate Dinneen Anne-Marie Baird Ciara Ryan Orla Sheils The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma Frontiers in Molecular Biosciences cancer stem cells drug resistance gastroesophageal junction adenocarcinoma epithelial mesenchymal transition microRNA |
| title | The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma |
| title_full | The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma |
| title_fullStr | The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma |
| title_full_unstemmed | The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma |
| title_short | The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma |
| title_sort | role of cancer stem cells in drug resistance in gastroesophageal junction adenocarcinoma |
| topic | cancer stem cells drug resistance gastroesophageal junction adenocarcinoma epithelial mesenchymal transition microRNA |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.600373/full |
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