Evidence map›Paper›PMID 41595180›Full record

ArticleCancers2026

Long-Read Spatial Transcriptomics of Patient-Derived Clear Cell Renal Cell Carcinoma Organoids Identifies Heterogeneity and Transcriptional Remodelling Following NUC-7738 Treatment.

Hazem Abdullah, Ying Zhang, Kathryn Kirkwood, Alexander Laird, Peter Mullen, David J Harrison, Mustafa Elshani

Abstract read
In one paragraph

Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Hazem AbdullahSchool of Medicine, University of St Andrews, North Haugh, St Andrews KY16 9TF, UK.ORCID 0009-0003-3476-6258
Ying ZhangSchool of Medicine, University of St Andrews, North Haugh, St Andrews KY16 9TF, UK.ORCID 0009-0002-2325-5412
Kathryn KirkwoodPathology, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK.
Alexander LairdEdinburgh Urological Cancer Group, Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK.ORCID 0000-0002-7296-025X
Peter MullenSchool of Medicine, University of St Andrews, North Haugh, St Andrews KY16 9TF, UK.ORCID 0000-0002-0841-609X
David J HarrisonSchool of Medicine, University of St Andrews, North Haugh, St Andrews KY16 9TF, UK.ORCID 0000-0001-9041-9988
Mustafa ElshaniSchool of Medicine, University of St Andrews, North Haugh, St Andrews KY16 9TF, UK.ORCID 0000-0002-2724-0325

Funding

European Union's Horizon 2020 research and innovation program 101017453Nucana (United Kingdom) No grant number
6 · The paper itself

Abstract

backgroundClear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and is marked by pronounced intra-tumoural heterogeneity that complicates therapeutic response. Patient-derived organoids offer a physiologically relevant model to capture this diversity and evaluate treatment effects. When integrated with spatial transcriptomics, they might enable the mapping of spatially resolved transcriptional and isoform-level changes within the tumour microenvironment.

methodsWe established a robust workflow for generating patient-derived ccRCC organoids, that are not passaged and retain original cellular components. These retain key features of the original tumours, including cancer cell, stromal, and immune components.

resultsSpatial transcriptomic profiling revealed multiple transcriptionally distinct regions within and across organoids, reflecting the intrinsic heterogeneity of ccRCC. Isoform-level analysis identified spatially variable expression of glutaminase (GLS) isoforms, with heterogeneous distributions of both the GAC and KGA variants. Treatment with NUC-7738, a phosphoramidate derivative of 3'-deoxyadenosine, induced marked transcriptional remodelling of organoids, including alterations in ribosomal and mitochondrial gene expression.

conclusionsThis study demonstrates that combining long-read spatial transcriptomics with patient-derived organoid models provides a powerful and scalable approach for dissecting gene and isoform-level heterogeneity in ccRCC and for elucidating spatially resolved transcriptional responses to novel therapeutics.

Indexed as

clear cell renal cell carcinomaheterogeneitylong read sequencingNUC-7738organoid spatial transcriptomicspatient-derived organoidstranscript isoforms

Identifiers

PMID41595180
PMCPMC12839147

What Socratic holds

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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 Socratic graph.