Evidence mapPaperPMID 39885295Full record

ArticleLeukemia2025

Targeting ABCD1-ACOX1-MET/IGF1R axis suppresses multiple myeloma.

Zhannan Han, Zhibo Yan, Zhehan Ma, Yihui Wang, Maja Beus, Junqi Lu, Loren B Weidenhammer, Kiran Lakhani, Jingyun Lee, John D Civils and 7 more

Abstract read
In one paragraph

Article in Leukemia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
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

17 authors.

Zhannan HanDepartment of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.
Zhibo YanDepartment of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.
Zhehan MaDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Yihui WangDepartment of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.ORCID 0009-0006-3693-2522
Maja BeusDepartment of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.ORCID 0000-0002-9619-7156
Junqi LuDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Loren B WeidenhammerDepartment of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.
Kiran LakhaniDepartment of Hematology and Medical Oncology Emory School of Medicine and the Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.
Jingyun LeeDepartment of Internal Medicine, Section of Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.
John D CivilsDepartment of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.
Cristina M FurduiDepartment of Internal Medicine, Section of Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.
Liang LiuDepartment of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.ORCID 0000-0001-8630-7430
Jian WuDivision of Hematologic Malignancies & Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
Yubin KangDivision of Hematologic Malignancies & Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
Erhard BieberichDepartment of Physiology, University of Kentucky College of Medicine, 741 S. Limestone BBSRB Room 269, Lexington, KY, 40536, USA.
Lawrence H BoiseDepartment of Hematology and Medical Oncology Emory School of Medicine and the Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.ORCID 0000-0001-9436-8815
Mikhail A NikiforovDepartment of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA. mikhail.nikiforov@duke.edu.ORCID 0000-0001-7868-0518

Funding

Women's Cancer ProgramP30CA014236 · NCI · DUKE UNIVERSITY · 1985 to 2025
$66.3M
Regulation and Function of Very Long Chain Fatty Acid Biosynthesis in Multiple MyelomaR01CA264984 · NCI · DUKE UNIVERSITY · 2023 to 2025
$772k
NCI NIH HHS R01 CA264984U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30CA014236U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA264984U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R21CA280499
6 · The paper itself

Abstract

Multiple myeloma (MM) remains an incurable hematological malignancy that necessitates the identification of novel therapeutic strategies. Here, we report that intracellular levels of very long chain fatty acids (VLCFAs) control the cytotoxicity of MM chemotherapeutic agents. Inhibition of VLCFA biosynthesis reduced cell death in MM cells caused by the proteasome inhibitor, bortezomib. Conversely, inhibition of VLCFA degradation via suppression of peroxisomal acyl-CoA oxidase 1 (ACOX1) increased the cytotoxicity of bortezomib, its next-generation analog, carfilzomib, and the immunomodulatory agent lenalidomide. Furthermore, treatment with an orally available ACOX1 inhibitor cooperated with bortezomib in suppressing the growth of bortezomib-resistant MM xenografts in mice. Increased VLCFA levels caused by genetic or pharmacological inhibition of VLCFA degradation reduced the activity of two major kinases involved in MM pathogenesis, MET proto-oncogene (MET) and insulin-like growth factor 1 receptor (IGF1R). Mechanistically, inhibition of ACOX1 promoted the accumulation of VLCFA-containing cerebrosides, altered MET and IGF1R interaction with a cerebroside analog, and selectively inhibited the association of these kinases with the plasma membrane signaling platforms, importantly, without disrupting the platforms' integrity. Our study revealed a specific metabolic vulnerability of MM cells and identified a targetable axis linking VLCFA metabolism to the regulation of MET and IGF1R activity.

Indexed as

Acyl-CoA OxidaseMultiple MyelomaProto-Oncogene Proteins c-metReceptor, IGF Type 1AnimalsAntineoplastic AgentsBortezomibCell Line, TumorDrug Resistance, NeoplasmHumansMiceProto-Oncogene MasSignal TransductionXenograft Model Antitumor AssaysAcyl-CoA OxidaseAntineoplastic AgentsBortezomibIGF1R protein, humanMAS1 protein, humanProto-Oncogene MasProto-Oncogene Proteins c-metReceptor, IGF Type 1

Identifiers

PMID39885295
PMCPMC12175649

What Socratic holds

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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 Socratic graph.