Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


10501.pdf (3.17 MB)

ETD Abstract Container

Abstract Header

Signaling Pathways Associated with Gefitinib Resistance in Glioblastoma Multiforme (GBM)

Aljohani, Hashim M., B.S.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406900804

Abstract Details

2014, MS, University of Cincinnati, Medicine: Molecular Genetics, Biochemistry, and Microbiology.
Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults and remains incurable despite multimodal intensive treatment regimens. The majority of GBM tumors show a mutated or overexpressed EGFR. However, the kinase domain mutations that usually correlate with response to the tyrosine kinase inhibitors in other cancers are infrequent in glioblastomas and phase II trials of the tyrosine kinase inhibitor (TKI), gefitinib showed no survival benefit in glioblastoma. Furthermore, tumors treated with the TKIs will inevitably recur highlighting the need to identify signaling pathways involved in GBM resistance to TKIs. To this end, we treated GBM cells that over express EGFR with increasing concentrations of Gefitinib and isolated resistant clones. These resistant clones were subject to RNAseq and the expression of several genes was found to be upregulated in these clones. These genes are all tyrosine kinase receptors and include ROS1, DDR1 and PDGFRA. The upregulation of these genes was confirmed at the protein level by western blot. Treatment with ROS1 inhibitors in ROS1 overexpressing clones led to sensitization of these clones to gefitinib. Our current study led to the discovery of alternative pathways used by GBM cells to evade cell death following treatment with gefitinib and identifies new therapeutic targets to prevent GBM cell resistance to the drug.
El Mustapha Bahassi, Ph.D. (Committee Chair)
Edmund Choi, Ph.D. (Committee Member)
Peter Stambrook, Ph.D. (Committee Member)
57 p.
Surgery
Glioblastoma multiforme; EGFR; tyrosine kinase inhibitor; GBM resistance to TKIs; Gefitinib; ROS1

Recommended Citations

Citations

  • Aljohani, H. M. (2014). Signaling Pathways Associated with Gefitinib Resistance in Glioblastoma Multiforme (GBM) [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406900804

    APA Style (7th edition)

  • Aljohani, Hashim. Signaling Pathways Associated with Gefitinib Resistance in Glioblastoma Multiforme (GBM). 2014. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406900804.

    MLA Style (8th edition)

  • Aljohani, Hashim. "Signaling Pathways Associated with Gefitinib Resistance in Glioblastoma Multiforme (GBM)." Master's thesis, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406900804

    Chicago Manual of Style (17th edition)

ucin1406900804
366
© 2014, some rights reserved.Creative Commons License Signaling Pathways Associated with Gefitinib Resistance in Glioblastoma Multiforme (GBM) by Hashim M. Aljohani B.S. is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.