In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids.
Tumour cells show a varying susceptibility to radiation damage as a function of the current cell cycle phase. While this sensitivity is averaged out in an unperturbed tumour due to unsynchronised cell cycle progression, external stimuli such as radiation or drug doses can induce a resynchronisation...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC3828142?pdf=render |
| _version_ | 1819010264980258816 |
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| author | Harald Kempf Haralampos Hatzikirou Marcus Bleicher Michael Meyer-Hermann |
| author_facet | Harald Kempf Haralampos Hatzikirou Marcus Bleicher Michael Meyer-Hermann |
| author_sort | Harald Kempf |
| collection | DOAJ |
| description | Tumour cells show a varying susceptibility to radiation damage as a function of the current cell cycle phase. While this sensitivity is averaged out in an unperturbed tumour due to unsynchronised cell cycle progression, external stimuli such as radiation or drug doses can induce a resynchronisation of the cell cycle and consequently induce a collective development of radiosensitivity in tumours. Although this effect has been regularly described in experiments it is currently not exploited in clinical practice and thus a large potential for optimisation is missed. We present an agent-based model for three-dimensional tumour spheroid growth which has been combined with an irradiation damage and kinetics model. We predict the dynamic response of the overall tumour radiosensitivity to delivered radiation doses and describe corresponding time windows of increased or decreased radiation sensitivity. The degree of cell cycle resynchronisation in response to radiation delivery was identified as a main determinant of the transient periods of low and high radiosensitivity enhancement. A range of selected clinical fractionation schemes is examined and new triggered schedules are tested which aim to maximise the effect of the radiation-induced sensitivity enhancement. We find that the cell cycle resynchronisation can yield a strong increase in therapy effectiveness, if employed correctly. While the individual timing of sensitive periods will depend on the exact cell and radiation types, enhancement is a universal effect which is present in every tumour and accordingly should be the target of experimental investigation. Experimental observables which can be assessed non-invasively and with high spatio-temporal resolution have to be connected to the radiosensitivity enhancement in order to allow for a possible tumour-specific design of highly efficient treatment schedules based on induced cell cycle synchronisation. |
| first_indexed | 2024-12-21T01:09:30Z |
| format | Article |
| id | doaj.art-f9afe6ce6f20486a9c516ccf97430c6e |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-21T01:09:30Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-f9afe6ce6f20486a9c516ccf97430c6e2022-12-21T19:20:58ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582013-01-01911e100329510.1371/journal.pcbi.1003295In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids.Harald KempfHaralampos HatzikirouMarcus BleicherMichael Meyer-HermannTumour cells show a varying susceptibility to radiation damage as a function of the current cell cycle phase. While this sensitivity is averaged out in an unperturbed tumour due to unsynchronised cell cycle progression, external stimuli such as radiation or drug doses can induce a resynchronisation of the cell cycle and consequently induce a collective development of radiosensitivity in tumours. Although this effect has been regularly described in experiments it is currently not exploited in clinical practice and thus a large potential for optimisation is missed. We present an agent-based model for three-dimensional tumour spheroid growth which has been combined with an irradiation damage and kinetics model. We predict the dynamic response of the overall tumour radiosensitivity to delivered radiation doses and describe corresponding time windows of increased or decreased radiation sensitivity. The degree of cell cycle resynchronisation in response to radiation delivery was identified as a main determinant of the transient periods of low and high radiosensitivity enhancement. A range of selected clinical fractionation schemes is examined and new triggered schedules are tested which aim to maximise the effect of the radiation-induced sensitivity enhancement. We find that the cell cycle resynchronisation can yield a strong increase in therapy effectiveness, if employed correctly. While the individual timing of sensitive periods will depend on the exact cell and radiation types, enhancement is a universal effect which is present in every tumour and accordingly should be the target of experimental investigation. Experimental observables which can be assessed non-invasively and with high spatio-temporal resolution have to be connected to the radiosensitivity enhancement in order to allow for a possible tumour-specific design of highly efficient treatment schedules based on induced cell cycle synchronisation.http://europepmc.org/articles/PMC3828142?pdf=render |
| spellingShingle | Harald Kempf Haralampos Hatzikirou Marcus Bleicher Michael Meyer-Hermann In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids. PLoS Computational Biology |
| title | In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids. |
| title_full | In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids. |
| title_fullStr | In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids. |
| title_full_unstemmed | In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids. |
| title_short | In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids. |
| title_sort | in silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids |
| url | http://europepmc.org/articles/PMC3828142?pdf=render |
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