Evidence map›Paper›PMID 30426838›Full record

ArticleMolecular pain

Expression of mitochondrial dysfunction-related genes and pathways in paclitaxel-induced peripheral neuropathy in breast cancer survivors.

Kord M Kober, Adam Olshen, Yvettte P Conley, Mark Schumacher, Kimberly Topp, Betty Smoot, Melissa Mazor, Margaret Chesney, Marilyn Hammer, Steven M Paul and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 8% of its field
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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.

  1. The Role of Oxidative Stress in Peripheral Neuropathy.Journal of molecular neuroscience : MN · 2020
    Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Mitochondrial AThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Applications of Cannabinoids in Neuropathic Pain: An Updated Review.Critical reviews in therapeutic drug carrier systems · 2024
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Cellular Pathogenesis of Chemotherapy-Induced Peripheral Neuropathy: Insights FromFrontiers in pain research (Lausanne, Switzerland) · 2022
    Review
  19. Article
  20. 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

12 authors at 3 institutions in 1 country.

Kord M Kober1 School of Nursing, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-9732-3321
Adam Olshen2 School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Yvettte P Conley3 School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA.
Mark Schumacher2 School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Kimberly Topp2 School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Betty Smoot2 School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Melissa Mazor1 School of Nursing, University of California, San Francisco, San Francisco, CA, USA.
Margaret Chesney2 School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Marilyn Hammer4 Department of Nursing, Mount Sinai Medical Center, New York, NY, USA.
Steven M Paul1 School of Nursing, University of California, San Francisco, San Francisco, CA, USA.
Jon D Levine2 School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Christine Miaskowski1 School of Nursing, University of California, San Francisco, San Francisco, CA, USA.
University of California, San Francisco · USMount Sinai Medical Center · USUniversity of Pittsburgh · US

Funding

Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
NCATS NIH HHS UL1 TR000004
6 · The paper itself

Abstract

backgroundPaclitaxel is one of the most commonly used drugs to treat breast cancer. Its major dose-limiting toxicity is paclitaxel-induced peripheral neuropathy (PIPN). PIPN persists into survivorship and has a negative impact on patient's mood, functional status, and quality of life. No interventions are available to treat PIPN. A critical barrier to the development of efficacious interventions is the lack of understanding of the mechanisms that underlie PIPN. Mitochondrial dysfunction has been evaluated in preclinical studies as a hypothesized mechanism for PIPN, but clinical data to support this hypothesis are limited. The purpose of this pilot study was to evaluate for differential gene expression and perturbed pathways between breast cancer survivors with and without PIPN.

methodsGene expression in peripheral blood was assayed using RNA-seq. Differentially expressed genes (DEG) and pathways associated with mitochondrial dysfunction were identified between survivors who received paclitaxel and did (n = 25) and did not (n = 25) develop PIPN.

resultsBreast cancer survivors with PIPN were significantly older; more likely to be unemployed; reported lower alcohol use; had a higher body mass index and poorer functional status; and had a higher number of lower extremity sites with loss of light touch, cold, and pain sensations and higher vibration thresholds. No between-group differences were found in the cumulative dose of paclitaxel received or in the percentage of patients who had a dose reduction or delay due to PIPN. Five DEGs and nine perturbed pathways were associated with mitochondrial dysfunction related to oxidative stress, iron homeostasis, mitochondrial fission, apoptosis, and autophagy.

conclusionsThis study is the first to provide molecular evidence that a number of mitochondrial dysfunction mechanisms identified in preclinical models of various types of neuropathic pain including chemotherapy-induced peripheral neuropathy are found in breast cancer survivors with persistent PIPN and suggest genes for validation and as potential therapeutic targets.

Indexed as

Cancer SurvivorsGene Expression RegulationBreast NeoplasmsFemaleHumansMiddle AgedMitochondriaPaclitaxelPainPeripheral Nervous System DiseasesSensationTranscriptomePaclitaxelbreast cancerdifferential gene expressionmitochondrianeuropathypaclitaxelpathway analysissurvivorTaxanes

Identifiers

PMID30426838
PMCPMC6293373
OpenAlexW2900633512

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.