Evidence map›Paper›PMID 37339930›Full record

ArticlePediatric blood & cancer2023

In vivo activity of the dual SYK/FLT3 inhibitor TAK-659 against pediatric acute lymphoblastic leukemia xenografts.

Keira Hughes, Kathryn Evans, Eric J Earley, Christopher M Smith, Stephen W Erickson, Tim Stearns, Vivek M Philip, Steven B Neuhauser, Jeffrey H Chuang, Emily L Jocoy and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Pediatric blood & cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

4 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. 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

14 authors at 4 institutions in 2 countries.

Keira HughesChildren's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW, Australia.
Kathryn EvansChildren's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW, Australia.
Eric J EarleyRTI International, Research Triangle Park, North Carolina, USA.ORCID https://orcid.org/0000-0001-6576-1319
Christopher M SmithChildren's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW, Australia.
Stephen W EricksonRTI International, Research Triangle Park, North Carolina, USA.
Tim StearnsThe Jackson Laboratory, Bar Harbor, Maine, USA.
Vivek M PhilipThe Jackson Laboratory, Bar Harbor, Maine, USA.
Steven B NeuhauserThe Jackson Laboratory, Bar Harbor, Maine, USA.
Jeffrey H ChuangThe Jackson Laboratory, Bar Harbor, Maine, USA.
Emily L JocoyThe Jackson Laboratory, Bar Harbor, Maine, USA.
Carol J BultThe Jackson Laboratory, Bar Harbor, Maine, USA.
Beverly A TeicherNational Cancer Institute, Bethesda, Maryland, USA.
Malcolm A SmithNational Cancer Institute, Bethesda, Maryland, USA.ORCID https://orcid.org/0000-0001-9880-9876
Richard B LockChildren's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW, Australia.ORCID https://orcid.org/0000-0002-3436-9071
Jackson Laboratory · USCancer Institute of New South Wales · AUNational Cancer Institute · USRTI International · US

Funding

Pediatric Preclinical Testing Consortium - LeukemiaU01CA199000 · NCI · UNIVERSITY OF NEW SOUTH WALES · PI Richard B Lock · 2015 to 2026
$4.8M
Pediatric Oncology In Vivo Testing Program Coordinating CenterU24CA263963 · NCI · JACKSON LABORATORY · PI CAROL J BULT, Jeffrey Hsu-Min Chuang · 2021 to 2026
$4.7M
Pediatric Preclinical Testing Consortium: Coordinating Center-Additional PPTC funding extensionU01CA199222 · NCI · RESEARCH TRIANGLE INSTITUTE · PI GATTO, GREGORY J · 2015 to 2021
$2.6M
NCI NIH HHS CA199000NCI NIH HHS CA199222NCI NIH HHS CA263963NCI NIH HHS U01 CA199000NCI NIH HHS U01 CA199222NCI NIH HHS U24 CA263963
6 · The paper itself

Abstract

backgroundWhile children with acute lymphoblastic leukemia (ALL) experience close to a 90% likelihood of cure, the outcome for certain high-risk pediatric ALL subtypes remains dismal. Spleen tyrosine kinase (SYK) is a prominent cytosolic nonreceptor tyrosine kinase in pediatric B-lineage ALL (B-ALL). Activating mutations or overexpression of Fms-related receptor tyrosine kinase 3 (FLT3) are associated with poor outcome in hematological malignancies. TAK-659 (mivavotinib) is a dual SYK/FLT3 reversible inhibitor, which has been clinically evaluated in several other hematological malignancies. Here, we investigate the in vivo efficacy of TAK-659 against pediatric ALL patient-derived xenografts (PDXs).

methodsSYK and FLT3 mRNA expression was quantified by RNA-seq. PDX engraftment and drug responses in NSG mice were evaluated by enumerating the proportion of human CD45

resultsFLT3 and SYK mRNA expression was significantly higher in B-lineage compared with T-lineage PDXs. TAK-659 was well tolerated and significantly prolonged the time to event in six out of eight PDXs tested. However, only one PDX achieved an objective response. The minimum mean %huCD45

conclusionsTAK-659 exhibited low to moderate single-agent in vivo activity against pediatric ALL PDXs representative of diverse subtypes.

Indexed as

FLT3mivavotinibpatient-derived xenograftspediatric acute lymphoblastic leukemiaSYKTAK-659

Identifiers

PMID37339930
PMCPMC10730772
OpenAlexW4381325522

What OpenQuestion holds

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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.