Evidence map›Paper›PMID 42779959›Full record

ArticlebioRxiv : the preprint server for biology2026

Metabolic Targeting of SREBP1 Reprograms the Obesity-Driven Ascites Immune Microenvironment and Enhances Chemotherapy Response in Obesity-Associated Ovarian Cancer.

Jing Yang, Tyvette S Hilliard, Yueying Liu, Emily Richardson, Sophia Santoso, Viktoriia Khomenko, Molly Conroy, Brandon Martin, Emily Cronberger, Gena Dominique and 5 more

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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

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

15 authors.

Jing YangDepartment of Chemistry & Biochemistry, University of Notre Dame, South Bend, IN, USA.
Tyvette S HilliardDepartment of Biology, Tuskegee University, Tuskegee, AL, USA.
Yueying LiuDepartment of Chemistry & Biochemistry, University of Notre Dame, South Bend, IN, USA.
Emily RichardsonHarper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA.
Sophia SantosoHarper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA.
Viktoriia KhomenkoHarper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA.
Molly ConroyHarper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA.
Brandon MartinHarper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA.
Emily CronbergerHarper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA.
Gena DominiqueDepartment of Chemistry & Biochemistry, University of Notre Dame, South Bend, IN, USA.
Zhikun WangDepartment of Chemistry & Biochemistry, University of Notre Dame, South Bend, IN, USA.
Jeffrey JohnsonDepartment of Chemistry & Biochemistry, University of Notre Dame, South Bend, IN, USA.
Wanrui WangDepartment of Chemistry & Biochemistry, University of Notre Dame, South Bend, IN, USA.
Ijeoma AsileboDepartment of Chemistry & Biochemistry, University of Notre Dame, South Bend, IN, USA.
M Sharon StackDepartment of Chemistry & Biochemistry, University of Notre Dame, South Bend, IN, USA.ORCID 0000-0003-4563-7390

Funding

Receptor Cross-Talk in Early Metastatic DisseminationR01CA109545 · NCI · UNIVERSITY OF NOTRE DAME · PI STACK, MARY SHARON · 2006 to 2022
$4.3M
The Impact of Maternal Obesity on the Reprogramming of the Metastatic MicroenvironmentK01CA218305 · NCI · UNIVERSITY OF NOTRE DAME · PI HILLIARD, TYVETTE · 2017 to 2021
$517k
NCI NIH HHS K01 CA218305NCI NIH HHS R01 CA109545
6 · The paper itself

Abstract

Obesity has an adverse effect on survival of women with ovarian cancer (OC), supporting a link between obesity, metastatic progression, and therapeutic response, but comprehensive mechanistic insight is lacking. In pre-clinical models of diet-induced obesity and OC, mice fed a high fat diet (HFD) exhibit substantially increased tumor burden relative to low fat diet (LFD) mice and respond poorly to standard-of-care (SOC) chemotherapy. Both HFD murine tumors and tumors from women with BMI>30 show increased expression and nuclear localization of sterol regulatory element binding protein 1 (SREBP1), a master regulator of lipogenesis and lipid transport. The objective of this study was to assess whether inhibition of SREBP1 processing could improve SOC chemotherapy response in obesity-associated OC. We evaluated the FDA-approved drug Nelfinavir (NFV), a pharmacologic inhibitor of site-2 protease that blocks SREBP1 processing, in combination with SOC (paclitaxel+carboplatin) chemotherapy in preclinical models of diet-induced obesity and OC. Our results demonstrate significantly improved therapeutic response, corresponding changes in intra-tumoral adipocytes, and reprogramming of the obesity-driven ascites immune microenvironment. These findings support a model in which NFV-mediated inhibition of SREBP1 processing disrupts obesity-associated metabolic pathways linked to immune suppression and therapeutic resistance, thereby enhancing response to SOC chemotherapy in obesity-associated OC. Collectively, these results highlight metabolic targeting as a strategy to improve therapeutic outcomes in obesity-associated ovarian cancer.

Indexed as

Fatostatinhigh fat dietimmune profileNelfinavirobesityovarian cancerSREBP1

Identifiers

PMID42779959
PMCPMC13596328

What OpenQuestion 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 OpenQuestion graph.