Evidence map›Paper›PMID 36316440›Full record

ArticleCommunications biology2022

Rewiring glucose metabolism improves 5-FU efficacy in p53-deficient/KRAS

Marlies C Ludikhuize, Sira Gevers, Nguyen T B Nguyen, Maaike Meerlo, S Khadijeh Shafiei Roudbari, M Can Gulersonmez, Edwin C A Stigter, Jarno Drost, Hans Clevers, Boudewijn M T Burgering and 1 more

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. 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

11 authors at 3 institutions in 1 country.

Marlies C LudikhuizeMolecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands.ORCID 0000-0002-7969-015X
Sira GeversMolecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands.
Nguyen T B NguyenMolecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands.
Maaike MeerloMolecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands.
S Khadijeh Shafiei RoudbariMolecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands.
M Can GulersonmezMolecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands.
Edwin C A StigterMolecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands.
Jarno DrostPrincess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.ORCID 0000-0002-2941-6179
Hans CleversPrincess Máxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.ORCID 0000-0002-3077-5582
Boudewijn M T BurgeringMolecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands.
Maria J Rodríguez ColmanMolecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands. m.j.rodriguezcolman@umcutrecht.nl.ORCID 0000-0001-8382-5128
University Medical Center Utrecht · NLRoyal Netherlands Academy of Arts and Sciences · NLOncode Institute · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite the fact that 5-fluorouracil (5-FU) is the backbone for chemotherapy in colorectal cancer (CRC), the response rates in patients is limited to 50%. The mechanisms underlying 5-FU toxicity are debated, limiting the development of strategies to improve its efficacy. How fundamental aspects of cancer, such as driver mutations and phenotypic heterogeneity, relate to the 5-FU response remains obscure. This largely relies on the limited number of studies performed in pre-clinical models able to recapitulate the key features of CRC. Here, we analyzed the 5-FU response in patient-derived organoids that reproduce the different stages of CRC. We find that 5-FU induces pyrimidine imbalance, which leads to DNA damage and cell death in the actively proliferating cancer cells deficient in p53. Importantly, p53-deficiency leads to cell death due to impaired cell cycle arrest. Moreover, we find that targeting the Warburg effect in KRAS

Indexed as

Colorectal NeoplasmsTumor Suppressor Protein p53FluorouracilGlucoseHumansProto-Oncogene Proteins p21(ras)FluorouracilGlucoseKRAS protein, humanProto-Oncogene Proteins p21(ras)Tumor Suppressor Protein p53

Identifiers

PMID36316440
PMCPMC9622833
OpenAlexW4307895009

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.