Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Kinomic exploration of temozolomide and radiation resistance in Glioblastoma multiforme xenolines
Radiotherapy and Oncology, Volume 111, No. 3, Year 2014
Notification
URL copied to clipboard!
Description
Background and purpose Glioblastoma multiforme (GBM) represents the most common and deadly primary brain malignancy, particularly due to temozolomide (TMZ) and radiation (RT) resistance. To better understand resistance mechanisms, we examined global kinase activity (kinomic profiling) in both treatment sensitive and resistant human GBM patient-derived xenografts (PDX or "xenolines"). Materials and methods Thirteen orthotopically-implanted xenolines were examined including 8 with known RT sensitivity/resistance, while 5 TMZ resistant xenolines were generated through serial TMZ treatment in vivo. Tumors were harvested, prepared as total protein lysates, and kinomically analyzed on a PamStation®12 high-throughput microarray platform with subsequent upstream kinase prediction and network modeling. Results Kinomic profiles indicated elevated tyrosine kinase activity associated with the radiation resistance phenotype, including FAK and FGFR1. Furthermore, network modeling showed VEGFR1/2 and c-Raf hubs could be involved. Analysis of acquired TMZ resistance revealed more kinomic variability among TMZ resistant tumors. Two of the five tumors displayed significantly altered kinase activity in the TMZ resistant xenolines and network modeling indicated PKC, JAK1, PI3K, CDK2, and VEGFR as potential mediators of this resistance. Conclusion GBM xenolines provide a phenotypic model for GBM drug response and resistance that when paired with kinomic profiling identified targetable pathways to inherent (radiation) or acquired (TMZ) resistance. © 2014 Elsevier Ireland Ltd. All rights reserved.
Authors & Co-Authors
Anderson, Joshua C.
United States, Birmingham
The University of Alabama at Birmingham
Duarte, Christine W.
United States, Scarborough
Maine Medical Center Research Institute
Welaya, Karim
United States, Birmingham
The University of Alabama at Birmingham
Egypt, Alexandria
Alexandria University
Rohrbach, Timothy D.
United States, Birmingham
The University of Alabama at Birmingham
Bredel, Markus
United States, Birmingham
The University of Alabama at Birmingham
Yang, Eddy S.
United States, Birmingham
The University of Alabama at Birmingham
Choradia, Nirmal V.
United States, Birmingham
The University of Alabama at Birmingham
Thottassery, Jaideep V.
United States, Birmingham
Southern Research
Yancey Gillespie, George
United States, Birmingham
The University of Alabama at Birmingham
Bonner, James A.
United States, Birmingham
The University of Alabama at Birmingham
Willey, Christopher D.
United States, Birmingham
The University of Alabama at Birmingham
Statistics
Citations: 37
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1016/j.radonc.2014.04.010
e-ISSN:
18790887
Research Areas
Cancer
Health System And Policy