Evidence map›Paper›PMID 36551714›Full record

ArticleCancers2022

Hyperthermia as a Potential Cornerstone of Effective Multimodality Treatment with Radiotherapy, Cisplatin and PARP Inhibitor in

Mohammed Khurshed, Elia Prades-Sagarra, Sarah Saleh, Peter Sminia, Johanna W Wilmink, Remco J Molenaar, Hans Crezee, Cornelis J F van Noorden

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.2field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 9 citations in OpenAlex.

  1. Genotoxicity of cancer therapies and the risk of secondary malignancies: toward personalized prevention.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Mohammed KhurshedDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0002-1611-1798
Elia Prades-SagarraDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0003-2834-967X
Sarah SalehDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Peter SminiaDepartment of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.ORCID 0000-0002-9531-5704
Johanna W WilminkDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
Remco J MolenaarDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.ORCID 0000-0001-5651-3997
Hans CrezeeDepartment of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0002-7474-0533
Cornelis J F van NoordenDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0002-6191-0505
Amsterdam University Medical Centers · NLNational Institute of Biology · SI

Funding

Academic Medical Center AMC2016.1-10460Dutch Cancer Society KWF-UVA 2014-6839Slovenian Research Agency ARRS P1-0245 and J3-2526
6 · The paper itself

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.

Indexed as

cisplatinD-2-hydroxyglutaratehyperthermiaisocitrate dehydrogenasePARPradiotherapy

Identifiers

PMID36551714
PMCPMC9777513
OpenAlexW4312140624

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.