Evidence map›Paper›PMID 39126272›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2024

FTY720/Fingolimod mitigates paclitaxel-induced Sparcl1-driven neuropathic pain and breast cancer progression.

Sandeep K Singh, Cynthia Weigel, Ryan D R Brown, Christopher D Green, Connor Tuck, Daniela Salvemini, Sarah Spiegel

Abstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. The EGR1/ZFP36 axis governs glycosphingolipid metabolic reprogramming in monocyte-derived macrophages in guillain-barré syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  6. Astrocyte Regulation of Spinal Circuit Function.Journal of neurochemistry · 2026
    Review
  7. Article
  8. Review
  9. NXC736, a Functional Antagonist of S1PMolecules (Basel, Switzerland) · 2025
    Article
  10. Article
  11. Article
  12. Review
  13. FTY720/Fingolimod mitigates paclitaxel-induced Sparcl1-driven neuropathic pain and breast cancer progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  14. 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

7 authors.

Sandeep K SinghDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.ORCID 0000-0002-8069-6452
Cynthia WeigelDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.ORCID 0000-0003-3132-4203
Ryan D R BrownDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.ORCID 0000-0003-2880-0301
Christopher D GreenDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.ORCID 0000-0002-7983-7449
Connor TuckDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.ORCID 0009-0007-8615-5984
Daniela SalveminiDepartment of Pharmacology and Physiology School of Medicine and Institute for Translational Neuroscience, Saint Louis University, St. Louis, Missouri, USA.ORCID 0000-0002-0612-4448
Sarah SpiegelDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.ORCID 0000-0003-0751-2634

Funding

U.S. Department of Defense (DOD) DoD W81XWH2010434
6 · The paper itself

Abstract

Paclitaxel is among the most active chemotherapy drugs for the aggressive triple negative breast cancer (TNBC). Unfortunately, it often induces painful peripheral neuropathy (CIPN), a major debilitating side effect. Here we demonstrate that in naive and breast tumor-bearing immunocompetent mice, a clinically relevant dose of FTY720/Fingolimod that targets sphingosine-1-phosphate receptor 1 (S1PR1), alleviated paclitaxel-induced neuropathic pain. FTY720 also significantly attenuated paclitaxel-stimulated glial fibrillary acidic protein (GFAP), a marker for activated astrocytes, and expression of the astrocyte-secreted synaptogenic protein Sparcl1/Hevin, a key regulator of synapse formation. Notably, the formation of excitatory synapses containing VGluT2 in the spinal cord dorsal horn induced by paclitaxel was also inhibited by FTY720 treatment, supporting the involvement of astrocytes and Sparcl1 in CIPN. Furthermore, in this TNBC mouse model that mimics human breast cancer, FTY720 administration also enhanced the anti-tumor effects of paclitaxel, leading to reduced tumor progression and lung metastasis. Taken together, our findings suggest that targeting the S1P/S1PR1 axis with FTY720 is a multipronged approach that holds promise as a therapeutic strategy for alleviating both CIPN and enhancing the efficacy of chemotherapy in TNBC treatment.

Indexed as

Fingolimod HydrochlorideNeuralgiaPaclitaxelAnimalsAntineoplastic Agents, PhytogenicAstrocytesCalcium-Binding ProteinsCell Line, TumorDisease ProgressionExtracellular Matrix ProteinsFemaleGlial Fibrillary Acidic ProteinHumansMiceSphingosine-1-Phosphate ReceptorsTriple Negative Breast NeoplasmsAntineoplastic Agents, PhytogenicCalcium-Binding ProteinsExtracellular Matrix ProteinsFingolimod HydrochlorideGlial Fibrillary Acidic ProteinPaclitaxelS1pr1 protein, mouseSparcl1 protein, mouseSphingosine-1-Phosphate Receptorsbreast cancerCIPNpaclitaxelsphingosine‐1‐phosphate receptor 1

Identifiers

PMID39126272
PMCPMC11607628

What OpenQuestion holds

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LicenceCC BY
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.