Evidence map›Paper›PMID 32438775›Full record

ArticleCells2020

DHA Affects Microtubule Dynamics Through Reduction of Phospho-TCTP Levels and Enhances the Antiproliferative Effect of T-DM1 in Trastuzumab-Resistant HER2-Positive Breast Cancer Cell Lines.

Silvia D'Amico, Ewa Krystyna Krasnowska, Isabella Manni, Gabriele Toietta, Silvia Baldari, Giulia Piaggio, Marco Ranalli, Alessandra Gambacurta, Claudio Vernieri, Flavio Di Giacinto and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2020. 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
1.8field-weighted citation impact, top 15% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. The Therapeutic Potential of Dihydroartemisinin in Cancer Treatment.International journal of molecular sciences · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024
    Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
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

13 authors at 5 institutions in 1 country.

Silvia D'AmicoNational Research Council of Italy, Institute of Translational Pharmacology (IFT-CNR), 00133 Rome, Italy.ORCID 0000-0002-9805-4589
Ewa Krystyna KrasnowskaNational Research Council of Italy, Institute of Translational Pharmacology (IFT-CNR), 00133 Rome, Italy.ORCID 0000-0001-9137-5446
Isabella ManniUOSD SAFU, Department of Research, Diagnosis and Innovative Technologies, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy.
Gabriele ToiettaTumor Immunology and Immunotherapy Unit, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy.ORCID 0000-0003-4182-2468
Silvia BaldariTumor Immunology and Immunotherapy Unit, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy.ORCID 0000-0001-7982-9468
Giulia PiaggioUOSD SAFU, Department of Research, Diagnosis and Innovative Technologies, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy.
Marco RanalliDepartment of Experimental Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Alessandra GambacurtaDepartment of Experimental Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Claudio VernieriMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.ORCID 0000-0003-1577-8176
Flavio Di GiacintoDepartment of Neuroscience, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
Francesca BernassolaDepartment of Experimental Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Filippo de BraudMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
Maria LucibelloNational Research Council of Italy, Institute of Translational Pharmacology (IFT-CNR), 00133 Rome, Italy.
Istituto di Farmacologia Traslazionale · ITUniversity of Rome Tor Vergata · ITIFOM · ITUniversità Cattolica del Sacro Cuore · ITUniversity of Milan · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Trastuzumab emtansine (T-DM1) is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugated to the microtubule-targeting agent emtansine (DM1). T-DM1 is an effective agent in the treatment of patients with HER2-positive breast cancer whose disease has progressed on the first-line trastuzumab containing chemotherapy. However, both primary and acquired tumour resistance limit its efficacy. Increased levels of the phosphorylated form of Translationally Controlled Tumour Protein (phospho-TCTP) have been shown to be associated with a poor clinical response to trastuzumab therapy in HER2-positive breast cancer. Here we show that phospho-TCTP is essential for correct mitosis in human mammary epithelial cells. Reduction of phospho-TCTP levels by dihydroartemisinin (DHA) causes mitotic aberration and increases microtubule density in the trastuzumab-resistant breast cancer cells HCC1954 and HCC1569. Combinatorial studies show that T-DM1 when combined with DHA is more effective in killing breast cells compared to the effect induced by any single agent. In an orthotopic breast cancer xenograft model (HCC1954), the growth of the tumour cells resumes after having achieved a complete response to T-DM1 treatment. Conversely, DHA and T-DM1 treatment induces a severe and irreversible cytotoxic effect, even after treatment interruption, thus, improving the long-term efficacy of T-DM1. These results suggest that DHA increases the effect of T-DM1 as poison for microtubules and supports the clinical development of the combination of DHA and T-DM1 for the treatment of aggressive HER2-overexpressing breast cancer.

Indexed as

Drug Resistance, NeoplasmAnimalsApoptosisArtemisininsBiomarkers, TumorBreast NeoplasmsCell Line, TumorCell ProliferationDNA DamageErb-b2 Receptor Tyrosine KinasesFemaleHumansMice, SCIDMicrotubulesMitosisOxidative StressArtemisininsartenimolBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReactive Oxygen SpeciesTPT1 protein, humanTpt1 protein, mouseTrastuzumabTumor Protein, Translationally-Controlled 1DHAHER2-positive breast cancerphospho-TCTPT-DM1

Identifiers

PMID32438775
PMCPMC7290969
OpenAlexW3026349337

What OpenQuestion holds

Textmetadata
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.