TY  - JOUR
A1  - Ronellenfitsch, Michael Wilfried
A1  - Zeiner, Pia Susan
A1  - Mittelbronn, Michel Guy André
A1  - Urban, Hans
A1  - Pietsch, Torsten
A1  - Reuter, Dirk
A1  - Senft, Christian
A1  - Steinbach, Joachim Peter
A1  - Westphal, Manfred
A1  - Harter, Patrick Nikolaus
T1  - Akt and mTORC1 signaling as predictive biomarkers for the EGFR antibody nimotuzumab in glioblastoma
T2  - Acta Neuropathologica Communications
N2  - Glioblastoma (GB) is the most frequent primary brain tumor in adults with a dismal prognosis despite aggressive treatment including surgical resection, radiotherapy and chemotherapy with the alkylating agent temozolomide. Thus far, the successful implementation of the concept of targeted therapy where a drug targets a selective alteration in cancer cells was mainly limited to model diseases with identified genetic drivers. One of the most commonly altered oncogenic drivers of GB and therefore plausible therapeutic target is the epidermal growth factor receptor (EGFR). Trials targeting this signaling cascade, however, have been negative, including the phase III OSAG 101-BSA-05 trial. This highlights the need for further patient selection to identify subgroups of GB with true EGFR-dependency. In this retrospective analysis of treatment-naïve samples of the OSAG 101-BSA-05 trial cohort, we identify the EGFR signaling activity markers phosphorylated PRAS40 and phosphorylated ribosomal protein S6 as predictive markers for treatment efficacy of the EGFR-blocking antibody nimotuzumab in MGMT promoter unmethylated GBs. Considering the total trial population irrespective of MGMT status, a clear trend towards a survival benefit from nimotuzumab was already detectable when tumors had above median levels of phosphorylated ribosomal protein S6. These results could constitute a basis for further investigations of nimotuzumab or other EGFR- and downstream signaling inhibitors in selected patient cohorts using the reported criteria as candidate predictive biomarkers.
KW  - Epidermal growth factor receptor
KW  - Mammalian target of rapamycin
KW  - Glioblastoma
KW  - Nimotuzumab
KW  - Biomarker
KW  - Targeted therapy
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47150
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-471507
SN  - 2051-5960
N1  - Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 6
IS  - 1, Art. 81
SP  - 1
EP  - 13
PB  - Biomed Central
CY  - London
ER  -