2013
DOI: 10.1158/1535-7163.mct-13-0052
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Combined Inhibition of HER1/EGFR and RAC1 Results in a Synergistic Antiproliferative Effect on Established and Primary Cultured Human Glioblastoma Cells

Abstract: Glioblastoma is the most frequent brain tumor of glial origin in adults. With the best available standard-ofcare, patients with this disease have a life expectancy of only approximately 15 months after diagnosis. Because the EGF receptor (HER1/EGFR) is one of the most commonly dysregulated oncogenes in glioblastoma, HER1/ EGFR-targeted agents, such as erlotinib, were expected to provide a therapeutic benefit. However, their application in the clinical setting failed. Seeking an explanation for this finding, we… Show more

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Cited by 51 publications
(57 citation statements)
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“…53 Inhibitors that suppress Rac1 activation are likely promising therapeutic partners for EGFR-targeted agents, like Erlotinib, in a combined treatment of glioblastoma. 54 Hence, as a specific GEF for Rac1, Tiam1 could be a potential therapeutic target in clinical cancer treatment.…”
Section: Discussionmentioning
confidence: 99%
“…53 Inhibitors that suppress Rac1 activation are likely promising therapeutic partners for EGFR-targeted agents, like Erlotinib, in a combined treatment of glioblastoma. 54 Hence, as a specific GEF for Rac1, Tiam1 could be a potential therapeutic target in clinical cancer treatment.…”
Section: Discussionmentioning
confidence: 99%
“…Sooman et al showed by bioinformatics and in vitro studies that camptothecin, a topoisomerase I inhibitor, and imatinib, a tyrosine kinase inhibitor, combined with a Rac1 inhibitor had a synergistic effect on human glioblastoma cell lines 40. Karpel-Massler et al also reported that the combination of erlotinib, an EGFR inhibitor, and a Rac1 inhibitor presented a synergistic effect on established glioma cell lines and primary glioblastoma cells 41. Collectively, several studies indicate that targeting Rac1 may be associated with a therapeutic benefit, although Rac1 is also involved in physiological events such as vessel permeability indicating that targeting Rac1 could lead to leaky vessels.…”
Section: Discussionmentioning
confidence: 99%
“…Cells were grown as described (20,21). Cells were obtained from the ATCC or Cell Line Services and authenticated by the provider.…”
Section: Methodsmentioning
confidence: 99%
“…To examine cellular proliferation, 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assays were performed as previously described (21). …”
Section: Methodsmentioning
confidence: 99%