Evidence map›Paper›PMID 41542490›Full record

ArticlebioRxiv : the preprint server for biology2026

Drug-tolerant persister cells reallocate carbon sources to fuel antioxidant metabolism for survival.

Melvin Li, Bradley Priem, Luke V Loftus, Michael J Betenbaugh, Kenneth J Pienta, Sarah R Amend

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Melvin LiCancer Ecology Center, The James Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0001-5264-384X
Bradley PriemDepartment of Chemical and Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Luke V LoftusCancer Ecology Center, The James Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Michael J BetenbaughDepartment of Chemical and Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Kenneth J PientaCancer Ecology Center, The James Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Sarah R AmendCancer Ecology Center, The James Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0002-5606-1262

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael T. Lewis · 2007 to 2026
$73.9M
Tumor microvesicle-mediated modulation of the bone microenvironmentP01CA093900 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KELLER, EVAN T · 2004 to 2024
$29.6M
TRANS_NETWORK PROJECTSU54CA143803 · NCI · PRINCETON UNIVERSITY · PI GETZENBERG, ROBERT H. · 2009 to 2013
$14.2M
Mechanisms That Regulate Dormancy of Disseminated Tumor Cells in the Bone MarrowU54CA163124 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHIOZAWA, YUSUKE · 2011 to 2015
$3.0M
Reactive Stroma and Tumor Associated Macrophages in Prostate Cancer ProgressionU01CA143055 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PIENTA, KENNETH J., ROWLEY, DAVID R · 2010 to 2014
$2.7M
NCI NIH HHS P01 CA093900NCI NIH HHS P30 CA125123NCI NIH HHS U01 CA143055NCI NIH HHS U54 CA143803NCI NIH HHS U54 CA163124
6 · The paper itself

Abstract

Therapy resistance is the leading cause of cancer-related deaths. Drug-tolerant persister cells (DTPs) represent a major barrier to cancer cure, mediating resistance through adaptive cell state transitions and driving tumor progression. Here, we investigate metabolic differences between DTPs and drug-sensitive cancer cells using integrated fluxomics. Proteomic profiling and extracellular flux analyses revealed that DTPs upregulate glycolysis and gluconeogenesis while reducing oxidative phosphorylation, indicating a shift in central carbon metabolism. Isotope tracing and metabolic modeling demonstrate that DTPs utilize glucose to fuel the pentose phosphate pathway (PPP) to generate NADPH and metabolize glutamine to provide carbons for the PPP via gluconeogenesis. Integrating our multi-omic datasets into a genome-scale model identified that DTPs sustain antioxidant metabolism by decreasing fluxes of other NADPH-consuming reactions upon

Indexed as

13C-metabolic flux analysisCancer metabolismDrug-tolerant persister cellsGenome scale metabolic modelingIntegrated fluxomics

Identifiers

PMID41542490
PMCPMC12803179

What Socratic 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 Socratic graph.