EGFR heterogeneity and implications for therapeutic intervention in glioblastoma

Eskil Eskilsson; Gro V. Røsland; Gergely Solecki; Qianghu Wang; Patrick N. Harter; Grazia Graziani; Roel G.W. Verhaak; Frank Winkler; Rolf Bjerkvig; Hrvoje Miletic

doi:10.1093/neuonc/nox191

EGFR heterogeneity and implications for therapeutic intervention in glioblastoma

Eskil Eskilsson, Gro V. Røsland, Gergely Solecki, Qianghu Wang, Patrick N. Harter, Grazia Graziani, Roel G.W. Verhaak, Frank Winkler, Rolf Bjerkvig, Hrvoje Miletic^*

^*Corresponding author for this work

Department of Cancer Research

Research output: Contribution to journal › Article › Research › peer-review

176 Citations (Scopus)

Abstract

Patients with glioblastoma (GBM) have a universally poor prognosis and are in urgent need of effective treatment strategies. Recent advances in sequencing techniques unraveled the complete genomic landscape of GBMs and revealed profound heterogeneity of individual tumors even at the single cell level. Genomic profiling has detected epidermal growth factor receptor (EGFR) gene alterations in more than half of GBMs. Major genetic events include amplification and mutation of EGFR. Yet, treatment strategies targeting EGFR have thus far failed in clinical trials. In this review, we discuss the clonal and functional heterogeneity of EGFRs in GBM development and critically reassess the potential of EGFRs as therapeutic targets.

Original language	English
Pages (from-to)	743-752
Number of pages	10
Journal	Neuro-Oncology
Volume	20
Issue number	6
DOIs	https://doi.org/10.1093/neuonc/nox191
Publication status	Published - 18 May 2018

Keywords

EGFR
angiogenesis
glioblastoma
invasion
targeted therapy
tumor heterogeneity

Access to Document

10.1093/neuonc/nox191

Cite this

@article{e48edaa15bae4afea1e3e1c3aa1a6ae4,

title = "EGFR heterogeneity and implications for therapeutic intervention in glioblastoma",

abstract = "Patients with glioblastoma (GBM) have a universally poor prognosis and are in urgent need of effective treatment strategies. Recent advances in sequencing techniques unraveled the complete genomic landscape of GBMs and revealed profound heterogeneity of individual tumors even at the single cell level. Genomic profiling has detected epidermal growth factor receptor (EGFR) gene alterations in more than half of GBMs. Major genetic events include amplification and mutation of EGFR. Yet, treatment strategies targeting EGFR have thus far failed in clinical trials. In this review, we discuss the clonal and functional heterogeneity of EGFRs in GBM development and critically reassess the potential of EGFRs as therapeutic targets.",

keywords = "EGFR, angiogenesis, glioblastoma, invasion, targeted therapy, tumor heterogeneity",

author = "Eskil Eskilsson and R{\o}sland, {Gro V.} and Gergely Solecki and Qianghu Wang and Harter, {Patrick N.} and Grazia Graziani and Verhaak, {Roel G.W.} and Frank Winkler and Rolf Bjerkvig and Hrvoje Miletic",

note = "Funding Information: This work was supported by the Research Council of Norway, the Norwegian Cancer Society, Helse Vest, Haukeland University Hospital, University of Bergen, the K. G. Jebsen Research Foundation, and a grant to G.G. from the Italian Association for Cancer Research (AIRC 2013 IG 14042). Publisher Copyright: {\textcopyright} The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved.",

year = "2018",

month = may,

day = "18",

doi = "10.1093/neuonc/nox191",

language = "English",

volume = "20",

pages = "743--752",

journal = "Neuro-Oncology",

issn = "1522-8517",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - EGFR heterogeneity and implications for therapeutic intervention in glioblastoma

AU - Eskilsson, Eskil

AU - Røsland, Gro V.

AU - Solecki, Gergely

AU - Wang, Qianghu

AU - Harter, Patrick N.

AU - Graziani, Grazia

AU - Verhaak, Roel G.W.

AU - Winkler, Frank

AU - Bjerkvig, Rolf

AU - Miletic, Hrvoje

N1 - Funding Information: This work was supported by the Research Council of Norway, the Norwegian Cancer Society, Helse Vest, Haukeland University Hospital, University of Bergen, the K. G. Jebsen Research Foundation, and a grant to G.G. from the Italian Association for Cancer Research (AIRC 2013 IG 14042). Publisher Copyright: © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved.

PY - 2018/5/18

Y1 - 2018/5/18

N2 - Patients with glioblastoma (GBM) have a universally poor prognosis and are in urgent need of effective treatment strategies. Recent advances in sequencing techniques unraveled the complete genomic landscape of GBMs and revealed profound heterogeneity of individual tumors even at the single cell level. Genomic profiling has detected epidermal growth factor receptor (EGFR) gene alterations in more than half of GBMs. Major genetic events include amplification and mutation of EGFR. Yet, treatment strategies targeting EGFR have thus far failed in clinical trials. In this review, we discuss the clonal and functional heterogeneity of EGFRs in GBM development and critically reassess the potential of EGFRs as therapeutic targets.

AB - Patients with glioblastoma (GBM) have a universally poor prognosis and are in urgent need of effective treatment strategies. Recent advances in sequencing techniques unraveled the complete genomic landscape of GBMs and revealed profound heterogeneity of individual tumors even at the single cell level. Genomic profiling has detected epidermal growth factor receptor (EGFR) gene alterations in more than half of GBMs. Major genetic events include amplification and mutation of EGFR. Yet, treatment strategies targeting EGFR have thus far failed in clinical trials. In this review, we discuss the clonal and functional heterogeneity of EGFRs in GBM development and critically reassess the potential of EGFRs as therapeutic targets.

KW - EGFR

KW - angiogenesis

KW - glioblastoma

KW - invasion

KW - targeted therapy

KW - tumor heterogeneity

UR - http://www.scopus.com/inward/record.url?scp=85047747064&partnerID=8YFLogxK

U2 - 10.1093/neuonc/nox191

DO - 10.1093/neuonc/nox191

M3 - Article

C2 - 29040782

AN - SCOPUS:85047747064

SN - 1522-8517

VL - 20

SP - 743

EP - 752

JO - Neuro-Oncology

JF - Neuro-Oncology

IS - 6

ER -

EGFR heterogeneity and implications for therapeutic intervention in glioblastoma

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this