Evidence map›Paper›PMID 36612255›Full record

ArticleCancers2022

Integrative Multi-OMICs Identifies Therapeutic Response Biomarkers and Confirms Fidelity of Clinically Annotated, Serially Passaged Patient-Derived Xenografts Established from Primary and Metastatic Pediatric and AYA Solid Tumors.

Pankita H Pandya, Asha Jacob Jannu, Khadijeh Bijangi-Vishehsaraei, Erika Dobrota, Barbara J Bailey, Farinaz Barghi, Harlan E Shannon, Niknam Riyahi, Nur P Damayanti, Courtney Young and 19 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

9 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Therapeutic Targeting of BET Proteins in Sarcoma.Molecular cancer therapeutics · 2025
    Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. 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

29 authors at 4 institutions in 1 country.

Pankita H PandyaDepartment of Pediatrics, Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.ORCID 0000-0002-2021-5821
Asha Jacob JannuDepartment of Biostatistics & Health Data Science Indiana, University School of Medicine, Indianapolis, IN 46202, USA.
Khadijeh Bijangi-VishehsaraeiDepartment of Pediatrics, Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Erika DobrotaDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Barbara J BaileyDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Farinaz BarghiDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Harlan E ShannonDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Niknam RiyahiDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Nur P DamayantiDepartment of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Courtney YoungDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Rada MalkoDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Ryli JusticeDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Eric AlbrightDepartment of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
George E SanduskyDepartment of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.ORCID 0000-0003-0769-057X
L Daniel WurtzDepartment of Orthopedics Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Christopher D CollierDepartment of Orthopedics Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Mark S MarshallDepartment of Pediatrics, Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Rosa I GallagherCenter for Applied Proteomics and Molecular Medicine, Institute for Biomedical Innovation, George Mason University, Manassas, VA 20110, USA.
Julia D WulfkuhleCenter for Applied Proteomics and Molecular Medicine, Institute for Biomedical Innovation, George Mason University, Manassas, VA 20110, USA.
Emanuel F PetricoinCenter for Applied Proteomics and Molecular Medicine, Institute for Biomedical Innovation, George Mason University, Manassas, VA 20110, USA.
Kathy CoyPreclinical Modeling and Therapeutics Core, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Melissa TrowbridgePreclinical Modeling and Therapeutics Core, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Anthony L SinnPreclinical Modeling and Therapeutics Core, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Jamie L RenbargerDepartment of Pediatrics, Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Michael J FergusonDepartment of Pediatrics, Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Kun HuangDepartment of Biostatistics & Health Data Science Indiana, University School of Medicine, Indianapolis, IN 46202, USA.
Jie ZhangDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
M Reza SaadatzadehDepartment of Pediatrics, Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.ORCID 0000-0002-7976-7970
Karen E PollokDepartment of Pediatrics, Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Indiana University School of MedicineGeorge Mason University · USIndiana University Health · USNeurological Surgery · US

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI David W Clapp · 1999 to 2026
$59.3M
Indiana Medical Scientist/Engineer Training ProgramT32GM077229 · NIGMS · INDIANA UNIVERSITY INDIANAPOLIS · PI GASTON, BENJAMIN, HERBERT, BRITTNEY-SHEA · 2008 to 2022
$6.0M
Indiana Clinical and Translational Sciences InstituteTL1TR001107 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$2.0M
Project 2: Biomarkers of endothelial dysfunction in pediatric patients receiving high intensity chemotherapy/irradiationP50HD090215 · NICHD · INDIANA UNIVERSITY INDIANAPOLIS · PI RENBARGER, JAMIE L · 2019 to 2020
$1.4M
Pediatric and Adult Translational Cancer Drug Discovery and Development Training Program (PACT-D3)T32CA272370 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI David W Clapp, Mark R. Kelley · 2023 to 2026
$569k
NCATS NIH HHS TL1 TR001107NCI NIH HHS P30 CA082709NCI NIH HHS P30CA082709NCI NIH HHS T32 CA272370NICHD NIH HHS P50 HD090215NIGMS NIH HHS T32 GM077229
6 · The paper itself

Abstract

Establishment of clinically annotated, molecularly characterized, patient-derived xenografts (PDXs) from treatment-naïve and pretreated patients provides a platform to test precision genomics-guided therapies. An integrated multi-OMICS pipeline was developed to identify cancer-associated pathways and evaluate stability of molecular signatures in a panel of pediatric and AYA PDXs following serial passaging in mice. Original solid tumor samples and their corresponding PDXs were evaluated by whole-genome sequencing, RNA-seq, immunoblotting, pathway enrichment analyses, and the drug−gene interaction database to identify as well as cross-validate actionable targets in patients with sarcomas or Wilms tumors. While some divergence between original tumor and the respective PDX was evident, majority of alterations were not functionally impactful, and oncogenic pathway activation was maintained following serial passaging. CDK4/6 and BETs were prioritized as biomarkers of therapeutic response in osteosarcoma PDXs with pertinent molecular signatures. Inhibition of CDK4/6 or BETs decreased osteosarcoma PDX growth (two-way ANOVA, p < 0.05) confirming mechanistic involvement in growth. Linking patient treatment history with molecular and efficacy data in PDX will provide a strong rationale for targeted therapy and improve our understanding of which therapy is most beneficial in patients at diagnosis and in those already exposed to therapy.

Indexed as

adolescents and young adults (AYA)BETsCDK4/6multi-OMICSosteosarcoma (OS)patient-derived xenografts (PDXs)pediatricprecision genomicsrhabdomyosarcoma (RMS)Wilms tumor

Identifiers

PMID36612255
PMCPMC9818438
OpenAlexW4313388771

What Socratic 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 Socratic graph.