Evidence map›Paper›PMID 41501085›Full record

ArticleNature communications2026

Loss of KDM6A-mediated genomic instability and metabolic reprogramming regulates response to therapeutic perturbations in bladder cancer.

Pratishtha Singh, Ranit D'Rozario, Bidisha Chakraborty, Swadhin Meher, Deblina Raychaudhuri, Aminah J Tannir, Yang Li, Anurag Majumdar, Jessalyn Hawkins, Yun Xiong and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Med Students SOAR: A Model for Immersive Oncology Research Training for Early Medical Trainees.Journal of cancer education : the official journal of the American Association for Cancer Education · 2026
    Article
  3. Review
  4. Review
  5. Article
  6. Review
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.

Pratishtha Singh *Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID http://orcid.org/0000-0002-9197-7241
Ranit D'Rozario *Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Bidisha Chakraborty *Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Swadhin Meher *Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Deblina RaychaudhuriDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Aminah J TannirDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Yang LiDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Anurag MajumdarDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jessalyn HawkinsDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Yun XiongDepartment of Bioinformatics and Computational Biology, Division, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Philip LorenziDepartment of Bioinformatics and Computational Biology, Division, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Padmanee SharmaDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID http://orcid.org/0000-0003-4658-055X
Kadir AkdemirDepartment of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Patrick PilieDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Abhinav K JainDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID http://orcid.org/0000-0003-3268-514X
Byron Hing Lung LeeDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID http://orcid.org/0000-0002-8755-9688
Sangeeta GoswamiDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. sgoswami@mdanderson.org.ORCID http://orcid.org/0000-0001-9201-4503

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Targeting epigenetic machinery to overcome myeloid cell-mediated resistance to anti-PD-1 therapy in GBMR37CA279192 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Sangeeta Goswami · 2023 to 2026
$1.9M
Medical Students Summer in Oncology at Anderson Research (Med Students SOAR) programR25CA265800 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Jillian Rebecca Gunther, Marites Pasuelo Melancon · 2023 to 2026
$1.3M
Super-Resolution OMX MicroscropeS10RR029552 · NCRR · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ZAL, TOMASZ · 2011 to 2011
$1.0M
Orbitrap Elite High-Resolution Mass Spectrometer for Proteomics and MetabolomicsS10OD012304 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HAWKE, DAVID H · 2013 to 2013
$877k
NCI NIH HHS P30 CA016672NCI NIH HHS R25 CA265800NCI NIH HHS R37 CA279192NCRR NIH HHS S10 RR029552NIH HHS S10 OD012304
6 · The paper itself

Abstract

Mutations in epigenetic regulators are common in bladder cancer, yet their impact on therapeutic responses remains unclear. Here, we identify that loss-of-function mutations in KDM6A, a histone demethylase altered in about 26% of advanced bladder cancers, are associated with poor survival after cisplatin chemotherapy, whereas they correlate with improved outcomes with anti-PD-1 therapy. Using CRISPR-Cas9-engineered murine and human bladder cancer models, we show that KDM6A deficiency increases formation of extrachromosomal circular DNA carrying chemoresistance loci, promoting cisplatin resistance. In parallel, KDM6A loss impairs DNA repair and rewires tumor metabolism, reducing glycolysis and lactate output. This metabolic shift diminishes histone lactylation in regulatory T cells, suppressing immunoregulatory genes and limiting expansion of PD-1

Indexed as

Genomic InstabilityHistone DemethylasesNuclear ProteinsUrinary Bladder NeoplasmsAnimalsCell Line, TumorCisplatinDNA RepairDrug Resistance, NeoplasmExtrachromosomal DNAHistonesHumansMetabolic ReprogrammingMiceMutationCisplatinExtrachromosomal DNAHistone DemethylasesHistonesKDM6A protein, humanNuclear Proteins

Identifiers

PMID41501085
PMCPMC12877084

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.