Evidence map›Paper›PMID 36291844›Full record

ArticleCancers2022

Inhibition of Phosphoglycerate Dehydrogenase Radiosensitizes Human Colorectal Cancer Cells under Hypoxic Conditions.

Melissa Van de Gucht, Inès Dufait, Lisa Kerkhove, Cyril Corbet, Sven de Mey, Heng Jiang, Ka Lun Law, Thierry Gevaert, Olivier Feron, Mark De Ridder

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 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.7field-weighted citation impact, top 35% 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

11 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. PHGDH: a novel therapeutic target in cancer.Experimental & molecular medicine · 2024
    Review
  10. Review
  11. 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

10 authors at 2 institutions in 1 country.

Melissa Van de GuchtDepartment of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.ORCID 0000-0002-8928-2985
Inès DufaitDepartment of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
Lisa KerkhoveDepartment of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.ORCID 0000-0003-2119-0520
Cyril CorbetPole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Mounier 53, 1200 Brussels, Belgium.ORCID 0000-0001-8795-9131
Sven de MeyDepartment of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.ORCID 0000-0001-8444-0836
Heng JiangDepartment of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
Ka Lun LawDepartment of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
Thierry GevaertDepartment of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.ORCID 0000-0003-4556-5681
Olivier FeronPole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Mounier 53, 1200 Brussels, Belgium.ORCID 0000-0001-5360-0286
Mark De RidderDepartment of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.ORCID 0000-0003-4433-8807
Vrije Universiteit Brussel · BEDirectorate-General Joint Research Centre · BE

Funding

Vrije Universiteit Brussel SRP53
6 · The paper itself

Abstract

Augmented de novo serine synthesis activity is increasingly apparent in distinct types of cancers and has mainly sparked interest by investigation of phosphoglycerate dehydrogenase (PHGDH). Overexpression of PHGDH has been associated with higher tumor grade, shorter relapse time and decreased overall survival. It is well known that therapeutic outcomes in cancer patients can be improved by reprogramming metabolic pathways in combination with standard treatment options, for example, radiotherapy. In this study, possible metabolic changes related to radioresponse were explored upon PHGDH inhibition. Additionally, we evaluated whether PHGDH inhibition could improve radioresponse in human colorectal cancer cell lines in both aerobic and radiobiological relevant hypoxic conditions. Dysregulation of reactive oxygen species (ROS) homeostasis and dysfunction in mitochondrial energy metabolism and oxygen consumption rate were indicative of potential radiomodulatory effects. We demonstrated that PHGDH inhibition radiosensitized hypoxic human colorectal cancer cells while leaving intrinsic radiosensitivity unaffected. In a xenograft model, the first hints of additive effects between PHGDH inhibition and radiotherapy were demonstrated. In conclusion, this study is the first to show that modulation of de novo serine biosynthesis enhances radioresponse in hypoxic colorectal cancer cells, mainly mediated by increased levels of intracellular ROS.

Indexed as

colorectal cancerhypoxiaradiosensitivityreactive oxygen speciesserine synthesis pathway

Identifiers

PMID36291844
PMCPMC9599856
OpenAlexW4306367202

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.