Tumor Treating Fields Alter the Kinomic Landscape in Glioblastoma Revealing Therapeutic Vulnerabilities

Amber B. Jones; Taylor L. Schanel; Mikayla R. Rigsby; Corinne E. Griguer; Braden C. McFarland; Joshua C. Anderson; Christopher D. Willey; Anita B. Hjelmeland

doi:10.3390/cells12172171

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Tumor Treating Fields Alter the Kinomic Landscape in Glioblastoma Revealing Therapeutic Vulnerabilities

Journal article

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Tumor Treating Fields Alter the Kinomic Landscape in Glioblastoma Revealing Therapeutic Vulnerabilities

Amber B. Jones, Taylor L. Schanel, Mikayla R. Rigsby, Corinne E. Griguer, Braden C. McFarland, Joshua C. Anderson, Christopher D. Willey and Anita B. Hjelmeland

Cells (Basel, Switzerland), Vol.12(17), 2171

08/30/2023

DOI: 10.3390/cells12172171

PMCID: PMC10486683

PMID: 37681903

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Abstract

Treatment for the deadly brain tumor glioblastoma (GBM) has been improved through the non-invasive addition of alternating electric fields, called tumor treating fields (TTFields). Improving both progression-free and overall survival, TTFields are currently approved for treatment of recurrent GBMs as a monotherapy and in the adjuvant setting alongside TMZ for newly diagnosed GBMs. These TTFields are known to inhibit mitosis, but the full molecular impact of TTFields remains undetermined. Therefore, we sought to understand the ability of TTFields to disrupt the growth patterns of and induce kinomic landscape shifts in TMZ-sensitive and -resistant GBM cells. We determined that TTFields significantly decreased the growth of TMZ-sensitive and -resistant cells. Kinomic profiling predicted kinases that were induced or repressed by TTFields, suggesting possible therapy-specific vulnerabilities. Serving as a potential pro-survival mechanism for TTFields, kinomics predicted the increased activity of platelet-derived growth-factor receptor alpha (PDGFRα). We demonstrated that the addition of the PDGFR inhibitor, crenolanib, to TTFields further reduced cell growth in comparison to either treatment alone. Collectively, our data suggest the efficacy of TTFields in vitro and identify common signaling responses to TTFields in TMZ-sensitive and -resistant populations, which may support more personalized medicine approaches.

Details

Title: Subtitle: Tumor Treating Fields Alter the Kinomic Landscape in Glioblastoma Revealing Therapeutic Vulnerabilities
Creators: Amber B. Jones - University of Alabama at Birmingham
Taylor L. Schanel - University of Alabama at Birmingham
Mikayla R. Rigsby - University of Alabama at Birmingham
Corinne E. Griguer - University of Iowa
Braden C. McFarland - University of Alabama at Birmingham
Joshua C. Anderson - University of Alabama at Birmingham
Christopher D. Willey - University of Alabama at Birmingham
Anita B. Hjelmeland - University of Alabama at Birmingham
Resource Type: Journal article
Publication Details: Cells (Basel, Switzerland), Vol.12(17), 2171
DOI: 10.3390/cells12172171
PMID: 37681903
PMCID: PMC10486683
NLM abbreviation: Cells
ISSN: 2073-4409
eISSN: 2073-4409
Publisher: MDPI
Grant note: NIH UAB startup funds In8Bio 20-60-62-WILL / 2020 AACR-Novocure Tumor Treating Fields Research Grant
Language: English
Date published: 08/30/2023
Academic Unit: Radiation Oncology
Record Identifier: 9984463082902771

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