Evidence map›Paper›PMID 28945796›Full record

ArticlePloS one2017

Cabozantinib and dastinib exert anti-tumor activity in alveolar soft part sarcoma.

Kenta Mukaihara, Yu Tanabe, Daisuke Kubota, Keisuke Akaike, Takuo Hayashi, Kaoru Mogushi, Masaki Hosoya, Shingo Sato, Eisuke Kobayashi, Taketo Okubo and 5 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 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
1.8field-weighted citation impact, top 14% 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, 24 citations in OpenAlex.

  1. Review
  2. Article
  3. The Recent Advances in Molecular Diagnosis of Soft Tissue Tumors.International journal of molecular sciences · 2023
    Review
  4. Article
  5. Review
  6. Clinical Activity of Single-Agent Cabozantinib (XL184), a Multi-receptor Tyrosine Kinase Inhibitor, in Patients with Refractory Soft-Tissue Sarcomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Article
  7. Article
  8. Article
  9. Article
  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

15 authors at 3 institutions in 1 country.

Kenta MukaiharaDepartment of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Yu TanabeDepartment of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Daisuke KubotaDepartment of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Keisuke AkaikeDepartment of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Takuo HayashiDepartment of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Kaoru MogushiCenter for Genomic and Regenerative Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Masaki HosoyaCenter for Genomic and Regenerative Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Shingo SatoDepartment of Physiology and Cell Biology, Tokyo Medical and Dental University Graduate School and Faculty of Medicine, Tokyo, Japan.
Eisuke KobayashiDivision of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan.
Taketo OkuboDepartment of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Youngji KimDepartment of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Shinji KohsakaDepartment of Medical Genomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Tsuyoshi SaitoDepartment of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Kazuo KanekoDepartment of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Yoshiyuki SueharaDepartment of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo, Japan.ORCID http://orcid.org/0000-0001-8206-3037
Juntendo University · JPThe University of Tokyo · JPTokyo Medical and Dental University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlveolar soft part sarcoma (ASPS) is an extremely rare metastatic soft tissue tumor with a poor prognosis for which no effective systemic therapies have yet been established. Therefore, the development of novel effective treatment approaches is required. Tyrosine kinases (TKs) are being increasingly used as therapeutic targets in a variety of cancers. The purpose of this study was to identify novel therapeutic target TKs and to clarify the efficacy of TK inhibitors (TKIs) in the treatment of ASPS. EXPERIMENTAL

designTo identify novel therapeutic target TKs in ASPS, we evaluated the antitumor effects and kinase activity of three TKIs (pazopanib, dasatinib, and cabozantinib) against ASPS cells using an in vitro assay. Based on these results, we then investigated the phosphorylation activities of the identified targets using western blotting, in addition to examining antitumor activity through in vivo assays of several TKIs to determine both the efficacy of these substances and accurate targets.

resultsIn cell proliferation and invasion assays using pazopanib, cabozantinib, and dasatinib, all three TKIs inhibited the cell growth in ASPS cells. Statistical analyses of the cell proliferation and invasion assays revealed that dasatinib had a significant inhibitory effect in cell proliferation assays, and cabozantinib exhibited marked inhibitory effects on cellular functions in both assays. Through western blotting, we also confirmed that cabozantinib inhibited c-MET phosphorylation and dasatinib inhibited SRC phosphorylation in dose-dependent fashion. Mice that received cabozantinib and dasatinib had significantly smaller tumor volumes than control animals, demonstrating the in vivo antitumor activity of, these substances.

conclusionsOur findings suggest that cabozantinib and dasatinib may be more effective than pazopanib against ASPS cells. These in vitro and in vivo data suggest that c-MET may be a potential therapeutic target in ASPS, and cabozantinib may be a particularly useful therapeutic option for patients with ASPS, including those with pazopanib-resistant ASPS.

Indexed as

AnilidesAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationDasatinibFemaleHumansIndazolesMiceMice, Inbred BALB CMice, NudeProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene Proteins c-metPyridinesAnilidesAntineoplastic AgentscabozantinibDasatinibIndazolesKDR protein, humanpazopanibProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene Proteins c-metPyridinesPyrimidinessrc-Family KinasesSulfonamidesVascular Endothelial Growth Factor Receptor-2

Identifiers

PMID28945796
PMCPMC5612696
OpenAlexW2759311891

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.