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01-10-2015 | Laboratory Investigation

Investigating a signature of temozolomide resistance in GBM cell lines using metabolomics

Authors: Patrick-Denis St-Coeur, Julie J. Poitras, Miroslava Cuperlovic-Culf, Mohamed Touaibia, Pier Jr Morin

Published in: Journal of Neuro-Oncology | Issue 1/2015

Abstract

Glioblastoma multiforme (GBM) is the most common form of malignant glioma. Current therapeutic approach to treat this malignancy involves a combination of surgery, radiotherapy and chemotherapy with temozolomide. Numerous mechanisms contributing to inherent and acquired resistance to this chemotherapeutic agent have been identified and can lead to treatment failure. This study undertook a metabolomics-based approach to characterize the metabolic profiles observed in temozolomide-sensitive and temozolomide-resistant GBM cell lines as well as in a small sub-set of primary GBM tumors. This approach was also utilized to explore the metabolic changes modulated upon cell treatment with temozolomide and lomeguatrib, an MGMT inhibitor with temozolomide-sensitizing potential. Metabolites previously explored for their potential role in chemoresistance including glucose, citrate and isocitrate demonstrated elevated levels in temozolomide-resistant GBM cells. In addition, a signature of metabolites comprising alanine, choline, creatine and phosphorylcholine was identified as up-regulated in sensitive GBM cell line across different treatments. These results present the metabolic profiles associated with temozolomide response in selected GBM models and propose interesting leads that could be leveraged for the development of therapeutic or diagnostic tools to impact temozolomide response in GBMs.

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Title: Investigating a signature of temozolomide resistance in GBM cell lines using metabolomics
Authors: Patrick-Denis St-Coeur
Julie J. Poitras
Miroslava Cuperlovic-Culf
Mohamed Touaibia
Pier Jr Morin
Publication date: 01-10-2015
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2015
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-015-1899-6

At a glance: The STEP trials

Springer Medicine

Investigating a signature of temozolomide resistance in GBM cell lines using metabolomics

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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