Evidence map›Paper›PMID 41102733›Full record

ArticleBreast cancer research : BCR2025

Biliverdin reductase B as a new target in breast cancer.

Natalia Marchenko, Natasha M Nesbitt, Evguenia Alexandrova, Julie A Reisz, Angelo D'Alessandro, Joonhyuk Suh, Stan Uryasev, Lisa Pennacchia, Wadie F Bahou

Abstract read
In one paragraph

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. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Natalia MarchenkoDepartment of Pathology, Stony Brook University, Stony Brook, NY, 11794, USA. natalia.marchenko@stonybrookmedicine.edu.
Natasha M NesbittBlood Cell Technologies, JLABS@NYC, 101 6th Avenue, New York, NY, 10013, USA.
Evguenia AlexandrovaDepartment of Pathology, Stony Brook University, Stony Brook, NY, 11794, USA.
Julie A ReiszDepartment of Biochemistry and Molecular Genetics, University of Colorado, Aurora, CO, 80045, USA.
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado, Aurora, CO, 80045, USA.
Joonhyuk SuhDepartment of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, 11794, USA.
Stan UryasevDepartment of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, 11794, USA.
Lisa PennacchiaBlood Cell Technologies, JLABS@NYC, 101 6th Avenue, New York, NY, 10013, USA.
Wadie F BahouDepartment of Medicine, Stony Brook University, Stony Brook, NY, 11794, USA.

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
The role of ferroptosis in red cell aging in vivo and in vitroR01HL146442 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Angelo D'Alessandro, Adam N. Goldfarb · 2019 to 2026
$5.4M
Development of a new class of BLVRB-targeted redox therapeutics in breast cancerR43CA284999 · NCI · BLOOD CELL TECHNOLOGIES, LLC · PI MARCHENKO, NATALIA · 2023 to 2023
$285k
NCI NIH HHS NCI CA284999NCI NIH HHS P30 CA046934NCI NIH HHS P30CA046934NCI NIH HHS R43 CA284999NHLBI NIH HHS R01 HL146442
6 · The paper itself

Abstract

backgroundEnhanced metabolic and mitochondrial activity inherent in actively proliferating cancer cells is associated with intracellular redox imbalance that impacts cellular viability. To restore redox homeostasis cancer cells evolve to activate redox protective mechanisms. This differential activation of redox defense pathways compared to normal cells provides a therapeutic window for novel targeted therapies in cancer. Although heme metabolism emerges as a crucial regulator of redox homeostasis and iron metabolism in cancer cells with frequent alteration in breast cancer, it remains largely unexplored, and no targeted translational approaches have been developed. Heme-regulated redox homeostasis is coordinately maintained through biosynthetic and degradation pathways. As a byproduct of TCA cycle, cytotoxic heme is initially derivatized by heme oxygenases and progressively metabolized to the potent antioxidant bilirubin by two non-redundant biliverdin reductases, BLVRA and BLVRB. BLVRB overexpression has been observed in breast cancers, although its function in breast cancer pathogenesis remains unknown.

methodsCRISPR/Cas9 deletion of BLVRB in multiple breast cancer cell lines demonstrated its profound effect on intracellular redox state and cell proliferation in vitro and in xenograft models. Integrated proteomic, metabolomic, and lipidomic studies identified and validated BLVRB-mediated adaptive metabolic responses required for breast cancer cell cytoprotection.

resultsWe have established BLVRB as a requisite component of the pro-survival redox defense mechanism in breast cancer cells. Targeted deletion of BLVRB induces reductive stress, leading to alterations in endoplasmic reticulum proteostasis and lipid composition. These defects impact plasma membrane functionality and endosomal recycling of multiple oncogenic receptors, such as HER2 and transferrin receptors.

conclusionsThese data collectively identify BLVRB as a novel metabolic target in breast cancer, distinct from other redox-regulating pathways. This study, along with our recent progress in developing novel specific BLVRB inhibitors, offers a unique translational opportunity for targeted therapies in personalized breast cancer medicine.

Indexed as

Breast NeoplasmsOxidoreductases Acting on CH-CH Group DonorsAnimalsCell Line, TumorCell ProliferationCRISPR-Cas SystemsFemaleHumansMiceOxidation-ReductionXenograft Model Antitumor Assaysbiliverdin reductaseOxidoreductases Acting on CH-CH Group DonorsHeme metabolismHER2 positive breast cancerRedox homeostasisTransferrin receptor

Identifiers

PMID41102733
PMCPMC12532840

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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.