Combining radiation to EGFR and Bcl-2 blockade : a new approach to target cancer stem cells in head and neck squamous cell carcinoma
PURPOSE: The clinical outcome of head and neck squamous cell carcinoma (HNSCC) remains poor, partly due to the presence of resistant cancer stem cells (CSCs) which are responsible of recurrences. CSCs have low EGFR expression and, conversely, overexpress the anti-apoptotic Bcl-2 protein, which is involved in resistance to apoptosis and the invasion/migration capacities of tumour cells.
METHODS: The combination therapy of ABT-199, a Bcl-2 inhibitor, cetuximab an EGFR inhibitor, and radiation using an HNSCC model (SQ20B cell line) and its corresponding CSC subpopulation were evaluated in vitro (2D/3D cell proliferation; invasion/migration and apoptosis using videomicroscopy) and in vivo.
RESULTS: Cetuximab strongly inhibited 2D and 3D cell proliferation, as well as invasion/migration, only in non-CSC-SQ20B cells, whereas ABT-199 selectively inhibited these mechanisms in SQ20B/CSCs. The combination of irradiation + cetuximab + ABT-199 increased the inhibition of the 2D and 3D cell proliferation, invasion/migration, and resistance to apoptosis in both cell sub-populations. In addition, in a nude mouse model with heterotopic tumour xenograft, a treatment combining cetuximab + ABT-199 with fractional irradiation strongly delayed the tumour growth and increased in vivo lifespan without side effects.
CONCLUSION: Based on the present results, this triple combination therapy may represent a new opportunity for testing in clinical trials, particularly in locally advanced HNSCC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:147 |
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| Enthalten in: |
Journal of cancer research and clinical oncology - 147(2021), 7 vom: 01. Juli, Seite 1905-1916 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guy, Jean-Baptiste [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.06.2021 Date Revised 07.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00432-021-03593-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM32347490X |
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| 100 | 1 | |a Guy, Jean-Baptiste |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Combining radiation to EGFR and Bcl-2 blockade |b a new approach to target cancer stem cells in head and neck squamous cell carcinoma |
| 264 | 1 | |c 2021 | |
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| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.06.2021 | ||
| 500 | |a Date Revised 07.06.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: The clinical outcome of head and neck squamous cell carcinoma (HNSCC) remains poor, partly due to the presence of resistant cancer stem cells (CSCs) which are responsible of recurrences. CSCs have low EGFR expression and, conversely, overexpress the anti-apoptotic Bcl-2 protein, which is involved in resistance to apoptosis and the invasion/migration capacities of tumour cells | ||
| 520 | |a METHODS: The combination therapy of ABT-199, a Bcl-2 inhibitor, cetuximab an EGFR inhibitor, and radiation using an HNSCC model (SQ20B cell line) and its corresponding CSC subpopulation were evaluated in vitro (2D/3D cell proliferation; invasion/migration and apoptosis using videomicroscopy) and in vivo | ||
| 520 | |a RESULTS: Cetuximab strongly inhibited 2D and 3D cell proliferation, as well as invasion/migration, only in non-CSC-SQ20B cells, whereas ABT-199 selectively inhibited these mechanisms in SQ20B/CSCs. The combination of irradiation + cetuximab + ABT-199 increased the inhibition of the 2D and 3D cell proliferation, invasion/migration, and resistance to apoptosis in both cell sub-populations. In addition, in a nude mouse model with heterotopic tumour xenograft, a treatment combining cetuximab + ABT-199 with fractional irradiation strongly delayed the tumour growth and increased in vivo lifespan without side effects | ||
| 520 | |a CONCLUSION: Based on the present results, this triple combination therapy may represent a new opportunity for testing in clinical trials, particularly in locally advanced HNSCC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ABT-199 | |
| 650 | 4 | |a Bcl-2 | |
| 650 | 4 | |a Cancer stem cells | |
| 650 | 4 | |a Cetuximab | |
| 650 | 4 | |a Epidermal growth factor receptor | |
| 650 | 4 | |a HNSCC | |
| 650 | 4 | |a Radiation therapy | |
| 650 | 7 | |a BCL2 protein, human |2 NLM | |
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| 650 | 7 | |a Cetuximab |2 NLM | |
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| 700 | 1 | |a Espenel, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Louati, Safa |e verfasserin |4 aut | |
| 700 | 1 | |a Gauthier, Arnaud |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia, Max-Adrien |e verfasserin |4 aut | |
| 700 | 1 | |a Vial, Nicolas |e verfasserin |4 aut | |
| 700 | 1 | |a Malésys, Céline |e verfasserin |4 aut | |
| 700 | 1 | |a Ardail, Dominique |e verfasserin |4 aut | |
| 700 | 1 | |a Alphonse, Gersende |e verfasserin |4 aut | |
| 700 | 1 | |a Wozny, Anne-Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Rodriguez-Lafrasse, Claire |e verfasserin |4 aut | |
| 700 | 1 | |a Magné, Nicolas |e verfasserin |4 aut | |
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