Evidence map›Paper›PMID 37054779›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2023

Preclinical validation of a novel therapeutic strategy for choroid plexus carcinoma.

Brice Martin, Tyler Garman, Madeline Laramee, Amy Wang, Xiaohu Zhang, Erin Beck, Kelli Wilson, Carleen Klumpp-Thomas, Crystal McKnight, Xin Xu and 5 more

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

Article in Journal of controlled release : official journal of the Controlled Release Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

5 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
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 5 institutions in 1 country.

Brice MartinDepartment of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address: brm4007@med.cornell.edu.
Tyler GarmanDepartment of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Madeline LarameeDepartment of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Amy WangDivision of National Toxicology, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Xiaohu ZhangDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Erin BeckDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Kelli WilsonDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Carleen Klumpp-ThomasDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Crystal McKnightDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Xin XuDivision of National Toxicology, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Natalie HagenDivision of National Toxicology, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
David HollandDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nadia DahmaneDepartment of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Craig J ThomasDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Mark SouweidaneDepartment of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA; Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
National Center for Advancing Translational Sciences · USNational Institutes of Health · USCornell University · USWeill Cornell Medicine · USNeurological Surgery · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Research Services Section (RSS)ZICTR000242 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI WILSON, KELLI · 2015 to 2025
$64.9M
HTS enabled examination of drug combinationsZIATR000047 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI THOMAS, CRAIG · 2015 to 2025
$7.1M
Intramural NIH HHS Z99 TR999999Intramural NIH HHS ZIA TR000047NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Choroid plexus carcinoma (CPC) is a rare infantile brain tumor with an aggressive clinical course that often leaves children with debilitating side effects due to aggressive and toxic chemotherapies. Development of novel therapeutical strategies for this disease have been extremely limited owing to the rarity of the disease and the paucity of biologically relevant substrates. We conducted the first high-throughput screen (HTS) on a human patient-derived CPC cell line (Children Cancer Hospital Egypt, CCHE-45) and identified 427 top hits highlighting key molecular targets in CPC. Furthermore, a combination screen with a wide variety of targets revealed multiple synergistic combinations that may pave the way for novel therapeutical strategies against CPC. Based on in vitro efficiency, central nervous system (CNS) penetrance ability and feasible translational potential, two combinations using a DNA alkylating or topoisomerase inhibitors in combination with an ataxia telangiectasia mutated and rad3 (ATR) inhibitor (topotecan/elimusertib and melphalan/elimusertib respectively) were validated in vitro and in vivo. Pharmacokinetic assays established increased brain penetrance with intra-arterial (IA) delivery over intra-venous (IV) delivery and demonstrated a higher CNS penetrance for the combination melphalan/elimusertib. The mechanisms of synergistic activity for melphalan/elimusertib were assessed through transcriptome analyses and showed dysregulation of key oncogenic pathways (e.g. MYC, mammalian target of rapamycin mTOR, p53) and activation of critical biological processes (e.g. DNA repair, apoptosis, hypoxia, interferon gamma). Importantly, IA administration of melphalan combined with elimusertib led to a significant increase in survival in a CPC genetic mouse model. In conclusion, this study is, to the best of our knowledge, the first that identifies multiple promising combinatorial therapeutics for CPC and emphasizes the potential of IA delivery for the treatment of CPC.

Indexed as

CarcinomaChoroid Plexus NeoplasmsAnimalsChildHumansMammalsMelphalanMiceTopotecanMelphalanTopotecanChemogenomicChoroid plexus carcinomaDrug discoveryIntra-arterial deliveryPediatric brain tumorsPharmacokinetic

Identifiers

PMID37054779
PMCPMC10174050
OpenAlexW4365482959

What OpenQuestion holds

Textmetadata
LicenceTDM
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.