Evidence map›Paper›PMID 40839139›Full record

SynthesisMetabolomics : Official journal of the Metabolomic Society2025

A systematic review of omics discovery studies to identify pertinent metabolic pathways for locally advanced rectal cancer in response to neoadjuvant chemoradiotherapy.

Aaron Kler, Matthew Fok, Gabrielle J Grundy, Marco Sciacovelli, Warwick B Dunn, Dale Vimalachandran

Abstract readSystematic Review
In one paragraph

Synthesis in Metabolomics : Official journal of the Metabolomic Society, 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. Targeting metabolic dependencies to reverse chemoradiotherapy resistance in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2026
    Article
  2. Multimodal prehabilitation in digestive oncology: a scoping review.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 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

6 authors.

Aaron KlerInstitute of Systems Biology, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. Aaron.kler@liverpool.ac.uk.
Matthew FokInstitute of Systems Biology, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Gabrielle J GrundyInstitute of Systems Biology, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Marco SciacovelliInstitute of Systems Biology, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Warwick B DunnDepartment of Biochemistry, Cell and Systems Biology, Centre for Metabolomics Research, Institute of Systems, Molecular, and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK.
Dale VimalachandranInstitute of Systems Biology, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLocally advanced rectal cancer (LARC) has variable responses to neoadjuvant therapy (NAT). Therefore, identifying changes in biological pathways involved when LARC is treated with NAT is crucial for developing treatments to improve clinical outcomes, as NAT is both variable and unpredictable. Although individual studies have attempted to discern how the response differs at a transcriptomic, proteomic and metabolomic level, there has not been a unifying systematic review discerning the key changes in metabolic pathways in this patient population. AIM OF REVIEW: This systematic review aims to understand how metabolomics, proteomics and transcriptomics can demonstrate how the perturbed metabolic pathways of the NAT response in LARC can provide targets for further clinical research. KEY SCIENTIFIC CONCEPTS OF REVIEW: Thirteen studies met the inclusion criteria, including seven metabolomic, five proteomic, and one transcriptomic study. Metabolomic analyses revealed consistent alterations in amino acid metabolism, the tricarboxylic acid (TCA) cycle, and glycerophospholipid metabolism. Proteomic findings supported these results, highlighting disruptions in glycolysis and gluconeogenesis. Joint pathway analysis demonstrated a strong correlation (r = 0.99, p < 0.0001) between metabolic changes observed across omics platforms. Key pathways such as alanine, branched-chain amino acid, and aspartate metabolism were commonly altered and may contribute to radio-resistance through enhanced energy production, reactive oxygen species (ROS) neutralization, and DNA repair mechanisms. The convergence of multi-omic data underscores the biological relevance of these metabolic reprogramming events. However, due to the limited availability of transcriptomic data meeting inclusion criteria, these findings are primarily driven by metabolomic and proteomic analyses, which constrains the extent of full multi-omic integration. Future studies should aim to validate these findings in clinical cohorts and explore how targeting these "survival" pathways could optimize treatment response in LARC.

Indexed as

ChemoradiotherapyMetabolic Networks and PathwaysMetabolomicsNeoadjuvant TherapyRectal NeoplasmsHumansProteomicsTranscriptomeMetabolicMetabolomicsNeoadjuvantRectal cancer

Identifiers

PMID40839139
PMCPMC12370562

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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.