Evidence map›Paper›PMID 41406946›Full record

ArticleCell reports. Medicine2025

Vesicle-mediated mitochondrial clearance presents an actionable metabolic vulnerability in triple-negative breast cancer.

Jody Vykoukal, Yihui Chen, Mingxin Zuo, Riccardo Ballarò, Monica J Hong, Hansini Krishna, Daniela B Rodriquez-Perera, Hiroyuki Katayama, Ehsan Irajizad, Ranran Wu and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. 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
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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

22 authors.

Jody VykoukalDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yihui ChenDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mingxin ZuoDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Riccardo BallaròDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Monica J HongDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hansini KrishnaDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Daniela B Rodriquez-PereraDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hiroyuki KatayamaDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ehsan IrajizadDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ranran WuDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ricardo A León-LetelierDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jennifer B DennisonDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Angelica M GutierrezBreast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Adriana Paulucci-HolthauzenDepartment of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Timothy C ThompsonGenitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Leona RuslingDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yining CaiDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Fu Chung HsiaoDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Soyoung ParkDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Banu ArunBreast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Samir HanashDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Johannes F FahrmannDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jffahrmann@mdanderson.org.

Funding

Targeting Non-Canonical STING Signaling to Treat SPOP Mutant Castration-Resistant Prostate CancerR01CA281727 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Timothy Charles Thompson · 2023 to 2026
$2.6M
Repurposing Glucosylceramide Synthase to Promote Mitochondrial Lethality and Potentiate an Anti-Tumor Immune Response in Triple-Negative Breast CancerR37CA269611 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Johannes F Fahrmann · 2023 to 2026
$1.9M
NCI NIH HHS R01 CA281727NCI NIH HHS R37 CA269611
6 · The paper itself

Abstract

Selective autophagy of mitochondria is known to promote cancer cell survival and progression, including in triple-negative breast cancer (TNBC). Here, we apply an integrated multi-omics approach together with functional experimental analyses to investigate metabolic adaptations that support mitochondrial quality control in TNBC. We detail a mitochondrial quality control mechanism, complementary to mitophagy, that is enabled by a program of heightened extracellular sphingomyelin salvaging in TNBC coupled with extracellular vesicle-mediated intracellular clearance of mitochondrial damage. Targeting of this onco-metabolic pathway via repurposing of eliglustat, a selective small molecule inhibitor of glucosylceramide synthase, results in ceramide-mediated compensatory mitophagy and cancer cell death in vitro and attenuates tumor growth and prolongs overall survival at clinically achievable doses in orthotopic syngeneic mouse models of TNBC as well as in human cell line-derived xenograft models. Our study defines an unexplored mechanism of aberrant sphingolipid metabolism that underlies an actionable metabolic vulnerability for anti-cancer treatment.

Indexed as

Extracellular VesiclesMitochondriaTriple Negative Breast NeoplasmsAnimalsAutophagyCell Line, TumorCeramidesFemaleGlucosyltransferasesHumansMiceMitophagySphingomyelinsXenograft Model Antitumor Assaysceramide glucosyltransferaseCeramidesGlucosyltransferasesSphingomyelinsautophagyeliglustatextracellular vesiclesglucosylceramide synthasemitochondriasphingolipidstriple-negative breast cancer

Identifiers

PMID41406946
PMCPMC12765847

What OpenQuestion holds

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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 OpenQuestion graph.