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Title:Hyperthermia as a potential cornerstone of effective multimodality treatment with radiotherapy, cisplatin and PARP inhibitor in IDH1-mutated cancer cells
Authors:ID Khurshed, Mohammed (Author)
ID Prades-Sagarra, Elia (Author)
ID Al Saleh, Sarah (Author)
ID Sminia, Peter (Author)
ID Wilmink, Johanna W (Author)
ID Molenaar, Remco J. (Author)
ID Crezee, Hans (Author)
ID Noorden, Cornelis J. F. van (Author)
Files:URL URL - Source URL, visit https://doi.org/10.3390/cancers14246228
 
.pdf PDF - Presentation file, download (2,26 MB)
MD5: 7647330C54A03C1C14AD2CA5BBA142A1
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo NIB - National Institute of Biology
Abstract:Mutations in the isocitrate dehydrogenase 1 (IDH1MUT) gene occur in various types of malignancies, including ~60% of chondrosarcomas, ~30% of intrahepatic cholangiocarcinomas and >80% of low-grade gliomas. IDH1MUT are causal in the development and progression of these types of cancer due to neomorphic production of the oncometabolite D-2-hydroxyglutarate (D-2HG). Intracellular accumulation of D-2HG has been implicated in suppressing homologous recombination and renders IDH1MUT cancer cells sensitive to DNA-repair-inhibiting agents, such as poly-(adenosine 5′-diphosphate–ribose) polymerase inhibitors (PARPi). Hyperthermia increases the efficacy of DNA-damaging therapies such as radiotherapy and platinum-based chemotherapy, mainly by inhibition of DNA repair. In the current study, we investigated the additional effects of hyperthermia (42 °C for 1 h) in the treatment of IDH1MUT HCT116 colon cancer cells and hyperthermia1080 chondrosarcoma cancer cells in combination with radiation, cisplatin and/or a PARPi on clonogenic cell survival, cell cycle distribution and the induction and repair of DNA double-strand breaks. We found that hyperthermia in combination with radiation or cisplatin induces an increase in double-strand breaks and cell death, up to 10-fold in IDH1MUT cancer cells compared to IDH1 wild-type cells. This vulnerability was abolished by the IDH1MUT inhibitor AGI-5198 and was further increased by the PARPi. In conclusion, our study shows that IDH1MUT cancer cells are sensitized to hyperthermia in combination with irradiation or cisplatin and a PARPi. Therefore, hyperthermia may be an efficacious sensitizer to cytotoxic therapies in tumors where the clinical application of hyperthermia is feasible, such as IDH1MUT chondrosarcoma of the extremities.
Keywords:isocitrate dehydrogenase, PARP, hyperthermia, D‐2‐hydroxyglutarate, radiotherapy, cisplatin
Publication status:Published
Publication version:Version of Record
Publication date:17.12.2022
Year of publishing:2022
Number of pages:str. [1]-13
Numbering:Vol. 14, iss. 24
PID:20.500.12556/DiRROS-19413 New window
UDC:576
ISSN on article:2072-6694
DOI:10.3390/cancers14246228 New window
COBISS.SI-ID:134747651 New window
Note:Nasl. z nasl. zaslona; Opis vira z dne 20. 12. 2022; Ostali avtorji: Elia Prades-Sagarra, Sarah Saleh, Peter Sminia, Johanna W. Wilmink, Remco J. Molenaar, Hans Crezee and Cornelis J. F. van Noorden; Št. članka: 6228;
Publication date in DiRROS:18.07.2024
Views:522
Downloads:318
Metadata:XML DC-XML DC-RDF
:
KHURSHED, Mohammed, PRADES-SAGARRA, Elia, AL SALEH, Sarah, SMINIA, Peter, WILMINK, Johanna W, MOLENAAR, Remco J., CREZEE, Hans and NOORDEN, Cornelis J. F. van, 2022, Hyperthermia as a potential cornerstone of effective multimodality treatment with radiotherapy, cisplatin and PARP inhibitor in IDH1-mutated cancer cells. Cancers [online]. 2022. Vol. 14, no. 24, p. 1–13. [Accessed 10 April 2025]. DOI 10.3390/cancers14246228. Retrieved from: https://dirros.openscience.si/IzpisGradiva.php?lang=eng&id=19413
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Record is a part of a journal

Title:Cancers
Shortened title:Cancers
Publisher:MDPI
ISSN:2072-6694
COBISS.SI-ID:517914137 New window

Document is financed by a project

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:P1-0245-2019
Name:Ekotoksiologija, toksikološka genomika in karcinogeneza
Funder:ARIS - Slovenian Research and Innovation Agency
Project number:J3-2526-2020
Name:Razkrivanje niše matičnih glioma celic v iskanju novih terapevtskih ciljev pri bolnikih z glioblastomom
Funder:Other - Other funder or multiple funders
Funding programme:Dutch Cancer Society
Project number:KWF-UVA 2014-6839, KWF AMC2016.1-10460

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

Language:Slovenian
Keywords:izocitrat dehidrogenaza, PARP, hipertemija, D‐2‐hidroksiglutarat, radioterapija, cisplatin


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