Evidence map›Paper›PMID 39427933›Full record

ArticleRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2025

A novel lineage-tracing tool reveals that hypoxic tumor cells drive tumor relapse after radiotherapy.

Apostolos Menegakis, Claire Vennin, Jonathan Ient, Arjan J Groot, Lenno Krenning, Rob Klompmaker, Anoek Friskes, Mila Ilic, Ala Yaromina, Rolf Harkes and 7 more

Abstract read
In one paragraph

Article in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2025. 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
–field-weighted citation impact
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.

  1. Article
  2. Two-color spheroid model for determining the OJournal of biological engineering · 2026
    Article
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

17 authors.

Apostolos MenegakisOncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherland; Department of Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands; Oncode Institute, Division of Tumor Biology and Tumor Immunology, the Netherlands. Electronic address: a.menegakis@nki.nl.
Claire VenninDivision of Molecular Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Jonathan IentDepartment of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, the Netherlands.
Arjan J GrootDepartment of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, the Netherlands.
Lenno KrenningOncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherland.
Rob KlompmakerOncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherland.
Anoek FriskesOncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherland.
Mila IlicOncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherland.
Ala YarominaThe M-Lab, Department of Precision Medicine, GROW - School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.
Rolf HarkesBioimaging Facility, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Bram van den BroekBioimaging Facility, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Jan Jakob SonkeDepartment of Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Monique De JongDepartment of Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Jolanda PiepersDepartment of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, the Netherlands.
Jacco van RheenenDivision of Molecular Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Marc A VooijsDepartment of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Centre, 6200 MD Maastricht, the Netherlands. Electronic address: marc.vooijs@maastrichtuniversity.nl.
René H MedemaOncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherland; Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands(2). Electronic address: r.h.medema-2@prinsesmaximacentrum.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTumor hypoxia imposes a main obstacle to the efficacy of anti-cancer therapy. Understanding the cellular dynamics of individual hypoxic cells before, during and post-treatment has been hampered by the technical inability to identify and trace these cells over time. METHODS AND MATERIALS: Here, we present a novel lineage-tracing reporter for hypoxic cells based on the conditional expression of a HIF1a-CreER

resultsWe validate the reporter in monolayer cultures and we show that tagged cells colocalize in spheroids and human tumor xenografts with the hypoxic marker pimonidazole. We found that irradiation of H1299-HIFcreUnaG spheroids leads to preferential outgrowth of cells from the hypoxic core. Similarly, in xenografts tumors, although initially UnaG-positive-cells coincide with pimonidazole-positive tumor areas and they are merely quiescent, upon irradiation UnaG-positive cells enrich in regrowing tumors and are mainly proliferative.

conclusionsCollectively, our data provide clear evidence that the hypoxic cells drive tumor relapse after irradiation.

Indexed as

Neoplasm Recurrence, LocalAnimalsCell LineageCell Line, TumorFlow CytometryHumansMiceSpheroids, CellularTumor Cells, CulturedTumor Hypoxia

Identifiers

PMID39427933
PMCPMC11718160

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Registered trials

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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.