Evidence map›Paper›PMID 40055794›Full record

ArticleBreast cancer research : BCR2025

Lipid metabolic reprogramming drives triglyceride storage and variable sensitivity to FASN inhibition in endocrine-resistant breast cancer cells.

Ashley V Ward, Duncan Riley, Kirsten E Cosper, Jessica Finlay-Schultz, Heather M Brechbuhl, Andrew E Libby, Kaitlyn B Hill, Rohan R Varshney, Peter Kabos, Michael C Rudolph and 1 more

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Article in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Ashley V WardDepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Duncan RileyDepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Kirsten E CosperDepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Jessica Finlay-SchultzDepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Heather M BrechbuhlAnschutz Medical Campus, School of Medicine, Division of Medical Oncology, University of Colorado, Aurora, CO, USA.
Andrew E LibbyAnschutz Medical Campus, School of Medicine, Division of Endocrinology, University of Colorado, Aurora, CO, USA.
Kaitlyn B HillUniversity of Oklahoma Health Sciences Center, Harold Hamm Diabetes Center, Oklahoma City, OK, USA.
Rohan R VarshneyUniversity of Oklahoma Health Sciences Center, Harold Hamm Diabetes Center, Oklahoma City, OK, USA.
Peter KabosAnschutz Medical Campus, School of Medicine, Division of Medical Oncology, University of Colorado, Aurora, CO, USA.
Michael C Rudolph *Anschutz Medical Campus, School of Medicine, Division of Endocrinology, University of Colorado, Aurora, CO, USA.
Carol A Sartorius *Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA. Carol.Sartorius@cuanschutz.edu.

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI JANINE A HIGGINS · 1995 to 2026
$32.6M
Novel dietary interventions for reducing obesity-associated breast cancerR01CA258766 · NCI · UNIVERSITY OF COLORADO DENVER · PI VICTORIA A CATENACCI, Peter Kabos · 2022 to 2026
$3.1M
Hormones and Tumor Initiating Cells in Human Breast CancersR01CA140985 · NCI · UNIVERSITY OF COLORADO DENVER · PI SARTORIUS, CAROL ANN · 2011 to 2020
$3.0M
Breast Cancer Research Foundation 23-144Foundation for the National Institutes of Health R01CA258766-03NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA140985NCI NIH HHS R01CA140985NCI NIH HHS R01 CA258766NIDDK NIH HHS P30 DK048520
6 · The paper itself

Abstract

backgroundLipid metabolic reprogramming is increasingly recognized as a hallmark of endocrine resistance in estrogen receptor-positive (ER+) breast cancer. In this study, we investigated alterations in lipid metabolism in ER + breast cancer cell lines with acquired resistance to common endocrine therapies and evaluated the efficacy of a clinically relevant fatty acid synthase (FASN) inhibitor.

methodsER + breast cancer cell lines resistant to Tamoxifen (TamR), Fulvestrant (FulvR), and long-term estrogen withdrawal (EWD) were derived. Global gene expression and lipidomic profiling were performed to compare parental and endocrine resistant cells. Lipid storage was assessed using Oil Red O (ORO) staining. The FASN inhibitor TVB-2640 was tested for its impact on lipid storage and cell growth.

resultsEndocrine resistant cells showed significant enrichment in lipid metabolism pathways and distinct lipidomic profiles, characterized by elevated triglyceride levels and enhanced cytoplasmic lipid droplets.

conclusionEndocrine resistant breast cancer cells undergo a metabolic shift toward increased triglyceride storage and PUFAs with high degrees of desaturation. While TVB-2640 reduced lipid storage in most conditions, it had limited effects on the growth of endocrine resistant breast cancer cells. Targeting specific lipid metabolic dependencies, particularly pathways that produce PUFAs, represents a potential therapeutic strategy in endocrine resistant breast cancer.

Indexed as

Breast NeoplasmsDrug Resistance, NeoplasmFatty Acid Synthase, Type ILipid MetabolismTriglyceridesAntineoplastic Agents, HormonalCell Line, TumorCell ProliferationFemaleFulvestrantGene Expression Regulation, NeoplasticHumansLipidomicsMetabolic ReprogrammingReceptors, EstrogenTamoxifenAntineoplastic Agents, HormonalFASN protein, humanFatty Acid Synthase, Type IFulvestrantReceptors, EstrogenTamoxifenTriglyceridesBreast cancerEndocrine resistance, lipid metabolismFatty acidFatty acid synthaseLipidomics

Identifiers

PMID40055794
PMCPMC11889759

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Registered trials

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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.