Evidence map›Paper›PMID 28666189›Full record

ArticleTranslational oncology2017

Oral Metronomic Topotecan Sensitizes Crizotinib Antitumor Activity in ALK

Libo Zhang, Bing Wu, Sylvain Baruchel

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

Article in Translational oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-weighted citation impact, top 28% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Article
  3. Multiple approaches to repurposing drugs for neuroblastoma.Bioorganic & medicinal chemistry · 2022
    Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. 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

3 authors at 2 institutions in 1 country.

Libo ZhangNew Agent and Innovative Therapy Program, The Hospital for Sick Children, Toronto, Canada; Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada.
Bing WuNew Agent and Innovative Therapy Program, The Hospital for Sick Children, Toronto, Canada; Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada.
Sylvain BaruchelNew Agent and Innovative Therapy Program, The Hospital for Sick Children, Toronto, Canada; Division of Hematology and Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Canada. Electronic address: sylvain.baruchel@sickkids.ca.
Hospital for Sick Children · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAnaplastic lymphoma kinase (ALK) inhibitor crizotinib has proven to be effective in the treatment of ALK-mutated neuroblastoma, but crizotinib resistance was commonly observed in patients. We aimed to overcome crizotinib resistance by combining with the MEK inhibitor trametinib or low-dose metronomic (LDM) topotecan in preclinical neuroblastoma models.

methodsWe selected a panel of neuroblastoma cell lines carrying various ALK genetic aberrations to assess the therapeutic efficacy on cell proliferation in vitro. Downstream signals of ALK activation, including phosphorylation of ERK1/2, Akt as well as HIF-1α expression were evaluated under normoxic and hypoxic conditions. Tumor growth inhibition was further assessed in NOD/SCID xenograft mouse models.

resultsAll NBL cell lines responded to crizotinib treatment but at variable ED50 levels, ranging from 0.25 to 5.58 μM. ALK-mutated cell lines SH-SY5Y, KELLY, LAN-5, and CHLA-20 are more sensitive than ALK wild-type cell lines. In addition, we demonstrated that under hypoxic conditions, all NBL cell lines showed marked decrease of ED50s when compared to normoxia except for KELLY cells. Taking into consideration the hypoxia sensitivity to crizotinib, combined treatment with crizotinib and LDM topotecan demonstrated a synergistic effect in ALK

conclusionsOral metronomic topotecan reversed crizotinib drug resistance in the ALK

Identifiers

PMID28666189
PMCPMC5491461
OpenAlexW2728549817

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.