Development and Optimisation of Tumour Treating Fields (TTFields) Delivery within 3D Primary Glioma Stem Cell-like Models of Spatial Heterogeneity
Glioblastoma is an aggressive, incurable brain cancer with poor five-year survival rates of around 13% despite multimodal treatment with surgery, DNA-damaging chemoradiotherapy and the recent addition of Tumour Treating Fields (TTFields). As such, there is an urgent need to improve our current under...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/16/5/863 |
| _version_ | 1797264755345326080 |
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| author | Callum G. Jones Aurelie Vanderlinden Ola Rominiyi Spencer J. Collis |
| author_facet | Callum G. Jones Aurelie Vanderlinden Ola Rominiyi Spencer J. Collis |
| author_sort | Callum G. Jones |
| collection | DOAJ |
| description | Glioblastoma is an aggressive, incurable brain cancer with poor five-year survival rates of around 13% despite multimodal treatment with surgery, DNA-damaging chemoradiotherapy and the recent addition of Tumour Treating Fields (TTFields). As such, there is an urgent need to improve our current understanding of cellular responses to TTFields using more clinically and surgically relevant models, which reflect the profound spatial heterogeneity within glioblastoma, and leverage these biological insights to inform the rational design of more effective therapeutic strategies incorporating TTFields. We have recently reported the use of preclinical TTFields using the inovitro<sup>TM</sup> system within 2D glioma stem-like cell (GSC) models and demonstrated significant cytotoxicity enhancement when co-applied with a range of therapeutically approved and preclinical DNA damage response inhibitors (DDRi) and chemoradiotherapy. Here we report the development and optimisation of preclinical TTFields delivery within more clinically relevant 3D scaffold-based primary GSC models of spatial heterogeneity, and highlight some initial enhancement of TTFields potency with temozolomide and clinically approved PARP inhibitors (PARPi). These studies, therefore, represent an important platform for further preclinical assessment of TTFields-based therapeutic strategies within clinically relevant 3D GSC models, aimed towards accelerating clinical trial implementation and the ultimate goal of improving the persistently dire survival rates for these patients. |
| first_indexed | 2024-04-25T00:33:56Z |
| format | Article |
| id | doaj.art-030c9a7a40294db4987e0da1216ac36b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-25T00:33:56Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-030c9a7a40294db4987e0da1216ac36b2024-03-12T16:40:37ZengMDPI AGCancers2072-66942024-02-0116586310.3390/cancers16050863Development and Optimisation of Tumour Treating Fields (TTFields) Delivery within 3D Primary Glioma Stem Cell-like Models of Spatial HeterogeneityCallum G. Jones0Aurelie Vanderlinden1Ola Rominiyi2Spencer J. Collis3Division of Clinical Medicine, University of Sheffield Medical School, Sheffield S10 2RX, UKDivision of Clinical Medicine, University of Sheffield Medical School, Sheffield S10 2RX, UKDivision of Clinical Medicine, University of Sheffield Medical School, Sheffield S10 2RX, UKDivision of Clinical Medicine, University of Sheffield Medical School, Sheffield S10 2RX, UKGlioblastoma is an aggressive, incurable brain cancer with poor five-year survival rates of around 13% despite multimodal treatment with surgery, DNA-damaging chemoradiotherapy and the recent addition of Tumour Treating Fields (TTFields). As such, there is an urgent need to improve our current understanding of cellular responses to TTFields using more clinically and surgically relevant models, which reflect the profound spatial heterogeneity within glioblastoma, and leverage these biological insights to inform the rational design of more effective therapeutic strategies incorporating TTFields. We have recently reported the use of preclinical TTFields using the inovitro<sup>TM</sup> system within 2D glioma stem-like cell (GSC) models and demonstrated significant cytotoxicity enhancement when co-applied with a range of therapeutically approved and preclinical DNA damage response inhibitors (DDRi) and chemoradiotherapy. Here we report the development and optimisation of preclinical TTFields delivery within more clinically relevant 3D scaffold-based primary GSC models of spatial heterogeneity, and highlight some initial enhancement of TTFields potency with temozolomide and clinically approved PARP inhibitors (PARPi). These studies, therefore, represent an important platform for further preclinical assessment of TTFields-based therapeutic strategies within clinically relevant 3D GSC models, aimed towards accelerating clinical trial implementation and the ultimate goal of improving the persistently dire survival rates for these patients.https://www.mdpi.com/2072-6694/16/5/863Tumour Treating FieldsTTFieldsglioblastomaglioma stem-like cells3D modelsDNA damage response inhibitors |
| spellingShingle | Callum G. Jones Aurelie Vanderlinden Ola Rominiyi Spencer J. Collis Development and Optimisation of Tumour Treating Fields (TTFields) Delivery within 3D Primary Glioma Stem Cell-like Models of Spatial Heterogeneity Cancers Tumour Treating Fields TTFields glioblastoma glioma stem-like cells 3D models DNA damage response inhibitors |
| title | Development and Optimisation of Tumour Treating Fields (TTFields) Delivery within 3D Primary Glioma Stem Cell-like Models of Spatial Heterogeneity |
| title_full | Development and Optimisation of Tumour Treating Fields (TTFields) Delivery within 3D Primary Glioma Stem Cell-like Models of Spatial Heterogeneity |
| title_fullStr | Development and Optimisation of Tumour Treating Fields (TTFields) Delivery within 3D Primary Glioma Stem Cell-like Models of Spatial Heterogeneity |
| title_full_unstemmed | Development and Optimisation of Tumour Treating Fields (TTFields) Delivery within 3D Primary Glioma Stem Cell-like Models of Spatial Heterogeneity |
| title_short | Development and Optimisation of Tumour Treating Fields (TTFields) Delivery within 3D Primary Glioma Stem Cell-like Models of Spatial Heterogeneity |
| title_sort | development and optimisation of tumour treating fields ttfields delivery within 3d primary glioma stem cell like models of spatial heterogeneity |
| topic | Tumour Treating Fields TTFields glioblastoma glioma stem-like cells 3D models DNA damage response inhibitors |
| url | https://www.mdpi.com/2072-6694/16/5/863 |
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