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Naslov:Hyperthermia as a potential cornerstone of effective multimodality treatment with radiotherapy, cisplatin and PARP inhibitor in IDH1-mutated cancer cells
Avtorji:ID Khurshed, Mohammed (Avtor)
ID Prades-Sagarra, Elia (Avtor)
ID Al Saleh, Sarah (Avtor)
ID Sminia, Peter (Avtor)
ID Wilmink, Johanna W (Avtor)
ID Molenaar, Remco J. (Avtor)
ID Crezee, Hans (Avtor)
ID Noorden, Cornelis J. F. van (Avtor)
Datoteke:URL URL - Izvorni URL, za dostop obiščite https://doi.org/10.3390/cancers14246228
 
.pdf PDF - Predstavitvena datoteka, prenos (2,26 MB)
MD5: 7647330C54A03C1C14AD2CA5BBA142A1
 
Jezik:Angleški jezik
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:Logo NIB - Nacionalni inštitut za biologijo
Povzetek: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.
Ključne besede:isocitrate dehydrogenase, PARP, hyperthermia, D‐2‐hydroxyglutarate, radiotherapy, cisplatin
Status publikacije:Objavljeno
Verzija publikacije:Objavljena publikacija
Datum objave:17.12.2022
Leto izida:2022
Št. strani:str. [1]-13
Številčenje:Vol. 14, iss. 24
PID:20.500.12556/DiRROS-19413 Novo okno
UDK:576
ISSN pri članku:2072-6694
DOI:10.3390/cancers14246228 Novo okno
COBISS.SI-ID:134747651 Novo okno
Opomba: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;
Datum objave v DiRROS:18.07.2024
Število ogledov:516
Število prenosov:313
Metapodatki:XML DC-XML DC-RDF
:
KHURSHED, Mohammed, PRADES-SAGARRA, Elia, AL SALEH, Sarah, SMINIA, Peter, WILMINK, Johanna W, MOLENAAR, Remco J., CREZEE, Hans in 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 [na spletu]. 2022. Vol. 14, no. 24, p. 1–13. [Dostopano 6 april 2025]. DOI 10.3390/cancers14246228. Pridobljeno s: https://dirros.openscience.si/IzpisGradiva.php?lang=slv&id=19413
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Gradivo je del revije

Naslov:Cancers
Skrajšan naslov:Cancers
Založnik:MDPI
ISSN:2072-6694
COBISS.SI-ID:517914137 Novo okno

Gradivo je financirano iz projekta

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:P1-0245-2019
Naslov:Ekotoksiologija, toksikološka genomika in karcinogeneza
Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:J3-2526-2020
Naslov:Razkrivanje niše matičnih glioma celic v iskanju novih terapevtskih ciljev pri bolnikih z glioblastomom
Financer:Drugi - Drug financer ali več financerjev
Program financ.:Dutch Cancer Society
Številka projekta:KWF-UVA 2014-6839, KWF AMC2016.1-10460

Licence

Licenca:CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:izocitrat dehidrogenaza, PARP, hipertemija, D‐2‐hidroksiglutarat, radioterapija, cisplatin


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