Addition of PARP1-inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse model
Background: Efficacy of current treatment options for cervical cancer require improvement. Previous in vitro studies have shown the enhancing effects of the addition of PARP1-inhibitors to chemoradiotherapy and thermoradiotherapy. The aim of our present study was to test efficacy of different combin...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | International Journal of Hyperthermia |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/02656736.2025.2450514 |
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| author | Marloes IJff Xionge Mei Enzo M. Scutigliani Hans M. Rodermond Gregor G. W. van Bochove Przemek M. Krawczyk Nicolaas A. P. Franken Lukas J. A. Stalpers Johannes Crezee Arlene L. Oei |
| author_facet | Marloes IJff Xionge Mei Enzo M. Scutigliani Hans M. Rodermond Gregor G. W. van Bochove Przemek M. Krawczyk Nicolaas A. P. Franken Lukas J. A. Stalpers Johannes Crezee Arlene L. Oei |
| author_sort | Marloes IJff |
| collection | DOAJ |
| description | Background: Efficacy of current treatment options for cervical cancer require improvement. Previous in vitro studies have shown the enhancing effects of the addition of PARP1-inhibitors to chemoradiotherapy and thermoradiotherapy. The aim of our present study was to test efficacy of different combinations of treatment modalities radiotherapy, cisplatin, hyperthermia and PARP1-inhibitors using in vitro tumor models, ex vivo treated patient samples and in vivo tumor models.Materials and Methods: In vitro clonogenic survival curves (0–6 Gy) show that PARP1-i (4–5 M Olaparib) enhances both chemoradiotherapy (0.3–0.5 µM cisplatin) and thermoradiotherapy (42 °C for 1 h) in SiHa, CaSki and HeLa cells. A cervical cancer mouse model and freshly obtained in-house developed patient-derived organoids were used to examine the effects of different treatment combinations. For the in vivo study, human cervical cancer (SiHa) cells were injected in the right hind leg of athymic nude mice. In vivo mouse experiments show that PARP1-i enhances thermoradiotherapy or chemoradiotherapy by reduction of tumor volumes. Five cycles of treatment were applied with the following doses per cycle: irradiation 3 Gy, hyperthermia 1 h at 42 °C, cisplatin at 2 mg/kg, and twice PARP1-i at 50 mg/kg.Results: Quadruple treatment, combining radiotherapy, hyperthermia, cisplatin and PARP1-i, was very effective but also lead to severe side effects causing severe weight loss and death. In contrast, thermoradiotherapy or chemoradiotherapy with addition of PARP1-i, were effective without serious side effects.Conclusion: The triple combinations are promising options for potentially more effective treatment of locally advanced cervical cancer without more toxicity. |
| format | Article |
| id | doaj-art-1737eff8d7ea4443af10559112685ed6 |
| institution | Kabale University |
| issn | 0265-6736 1464-5157 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | International Journal of Hyperthermia |
| spelling | doaj-art-1737eff8d7ea4443af10559112685ed62025-01-21T23:11:41ZengTaylor & Francis GroupInternational Journal of Hyperthermia0265-67361464-51572025-12-0142110.1080/02656736.2025.2450514Addition of PARP1-inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse modelMarloes IJff0Xionge Mei1Enzo M. Scutigliani2Hans M. Rodermond3Gregor G. W. van Bochove4Przemek M. Krawczyk5Nicolaas A. P. Franken6Lukas J. A. Stalpers7Johannes Crezee8Arlene L. Oei9Laboratory for Experimental Oncology and Radiobiology (LEXOR), Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology (LEXOR), Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The NetherlandsCancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology (LEXOR), Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology (LEXOR), Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The NetherlandsCancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology (LEXOR), Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology (LEXOR), Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Radiation Oncology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology (LEXOR), Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The NetherlandsBackground: Efficacy of current treatment options for cervical cancer require improvement. Previous in vitro studies have shown the enhancing effects of the addition of PARP1-inhibitors to chemoradiotherapy and thermoradiotherapy. The aim of our present study was to test efficacy of different combinations of treatment modalities radiotherapy, cisplatin, hyperthermia and PARP1-inhibitors using in vitro tumor models, ex vivo treated patient samples and in vivo tumor models.Materials and Methods: In vitro clonogenic survival curves (0–6 Gy) show that PARP1-i (4–5 M Olaparib) enhances both chemoradiotherapy (0.3–0.5 µM cisplatin) and thermoradiotherapy (42 °C for 1 h) in SiHa, CaSki and HeLa cells. A cervical cancer mouse model and freshly obtained in-house developed patient-derived organoids were used to examine the effects of different treatment combinations. For the in vivo study, human cervical cancer (SiHa) cells were injected in the right hind leg of athymic nude mice. In vivo mouse experiments show that PARP1-i enhances thermoradiotherapy or chemoradiotherapy by reduction of tumor volumes. Five cycles of treatment were applied with the following doses per cycle: irradiation 3 Gy, hyperthermia 1 h at 42 °C, cisplatin at 2 mg/kg, and twice PARP1-i at 50 mg/kg.Results: Quadruple treatment, combining radiotherapy, hyperthermia, cisplatin and PARP1-i, was very effective but also lead to severe side effects causing severe weight loss and death. In contrast, thermoradiotherapy or chemoradiotherapy with addition of PARP1-i, were effective without serious side effects.Conclusion: The triple combinations are promising options for potentially more effective treatment of locally advanced cervical cancer without more toxicity.https://www.tandfonline.com/doi/10.1080/02656736.2025.2450514Cervical cancerhyperthermiaradiotherapychemotherapyparp1-inhibition |
| spellingShingle | Marloes IJff Xionge Mei Enzo M. Scutigliani Hans M. Rodermond Gregor G. W. van Bochove Przemek M. Krawczyk Nicolaas A. P. Franken Lukas J. A. Stalpers Johannes Crezee Arlene L. Oei Addition of PARP1-inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse model International Journal of Hyperthermia Cervical cancer hyperthermia radiotherapy chemotherapy parp1-inhibition |
| title | Addition of PARP1-inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse model |
| title_full | Addition of PARP1-inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse model |
| title_fullStr | Addition of PARP1-inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse model |
| title_full_unstemmed | Addition of PARP1-inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse model |
| title_short | Addition of PARP1-inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse model |
| title_sort | addition of parp1 inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse model |
| topic | Cervical cancer hyperthermia radiotherapy chemotherapy parp1-inhibition |
| url | https://www.tandfonline.com/doi/10.1080/02656736.2025.2450514 |
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