Evidence map›Paper›PMID 20159940›Full record

ReviewMolecular pharmacology2010

Copper transporters and the cellular pharmacology of the platinum-containing cancer drugs.

Stephen B Howell, Roohangiz Safaei, Christopher A Larson, Michael J Sailor

Open access · bronzeAbstract readReview
In one paragraph

Review in Molecular pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
152citing papers in PubMed, 1 pooled it
22.2field-weighted citation impact, top 1% 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

152 citing papers in PubMed, 1 synthesis or guideline pooled it, 337 citations in OpenAlex.

  1. Pooled it
  2. Trial
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  16. Therapeutic Potential of Metal-Based and PARP Inhibitor Chemotherapy forInternational journal of molecular sciences · 2025
    Review
  17. Review
  18. MiRNAs: main players of cancer drug resistance target ABC transporters.Naunyn-Schmiedeberg's archives of pharmacology · 2025
    Review
  19. Article
  20. Article

92 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

Stephen B HowellDepartment of Medicine, Moores UCSD Cancer Center, 3855 Health Sciences Drive, La Jolla, CA 92093, USA. showell@ucsd.edu.
Roohangiz Safaei
Christopher A Larson
Michael J Sailor
University of California, San Diego · US

Funding

Cisplatin Resistance mediated by copper export pathwaysR01CA095298 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HOWELL, STEPHEN B · 2002 to 2014
$3.1M
NCI NIH HHS R01 CA095298
6 · The paper itself

Abstract

Multiple lines of evidence indicate that the platinum-containing cancer drugs enter cells, are distributed to various subcellular compartments, and are exported from cells via transporters that evolved to manage copper homeostasis. The cytotoxicity of the platinum drugs is directly related to how much drug enters the cell, and almost all cells that have acquired resistance to the platinum drugs exhibit reduced drug accumulation. The major copper influx transporter, copper transporter 1 (CTR1), has now been shown to control the tumor cell accumulation and cytotoxic effect of cisplatin, carboplatin, and oxaliplatin. There is a good correlation between change in CTR1 expression and acquired cisplatin resistance among ovarian cancer cell lines, and genetic knockout of CTR1 renders cells resistant to cisplatin in vivo. The expression of CTR1 is regulated at the transcriptional level by copper via Sp1 and at the post-translational level by the proteosome. Copper and cisplatin both trigger the down-regulation of CTR1 via a process that involves ubiquitination and proteosomal degradation and requires the copper chaperone antioxidant protein 1 (ATOX1). The cisplatin-induced degradation of CTR1 can be blocked with the proteosome inhibitor bortezomib, and this increases the cellular uptake and the cytotoxicity of cisplatin in a synergistic manner. Copper and platinum(II) have similar sulfur binding characteristics, and the presence of stacked rings of methionines and cysteines in the CTR1 trimer suggest a mechanism by which CTR1 selectively transports copper and the platinum-containing drugs via sequential transchelation reactions similar to the manner in which copper is passed from ATOX1 to the copper efflux transporters.

Indexed as

Antineoplastic AgentsCarboplatinCation Transport ProteinsCisplatinCopperCopper Transporter 1Gene Expression RegulationHomeostasisHumansOrganoplatinum CompoundsOxaliplatinProtein ConformationAntineoplastic AgentsCarboplatinCation Transport ProteinsCisplatinCopperCopper Transporter 1Organoplatinum CompoundsOxaliplatinSLC31A1 protein, human

Identifiers

PMID20159940
PMCPMC3202487
OpenAlexW2096510511

What OpenQuestion holds

Textmetadata
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.