EGFRvIII mutations can emerge as late and heterogenous events in glioblastoma development and promote angiogenesis through Src activation

Eskilsson, Eskil; Røsland, Gro Vatne; Talasila, Krishna M.; Knappskog, Stian; Keunen, Olivier; Sottoriva, Andrea; Foerster, Sarah; Solecki, Gergely; Taxt, Torfinn; Jiřík, Radovan; Fritah, Sabrina; Harter, Patrick N.; Välk, Kristjan; Hossain, Jubayer A; Joseph, Justin V.; Jahedi, Roza Z.; Saed, Halala; Piccirillo, Sara Grazia Maria; Spiteri, Inma; Leiss, Lina; Euskirchen, Philipp; Graziani, Grazia; Daubon, Thomas; Lund‐Johansen, Morten; Enger, Per Øyvind; Winkler, Frank; Ritter, Christoph A.; Niclou, Simone P.; Watts, Colin; Bjerkvig, Rolf; Miletić, Hrvoje

doi:10.1093/neuonc/now113

Cited by 84 publications

(91 citation statements)

References 43 publications

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“…However, previous studies reported that EGFR amplification may be restricted to subpopulations of tumor cells, as determined in cases of glioblastomas with amplification of EGFR and PDGFRA (52,53). With respect to EGFRvIII expression, our data demonstrate that EGFRvIII immunopositivity shows marked regional heterogeneity and is often restricted to subpopulations of tumor cells in glioblastomas, thus confirming previous findings in the GGN patient cohort (17) and in several independent studies (39,42,43,51,54).…”

Section: Discussionsupporting

confidence: 91%

“…Accumulating preclinical evidence has attributed an important function of EGFRvIII-expressing glioblastoma cells in driving tumor heterogeneity and progression by promoting glioma cell proliferation, invasion, angiogenesis, stemness, and therapy resistance in different model systems (36)(37)(38)(39)(40)(41)(42)(43). In addition, several therapeutic approaches targeting overexpressed wild type EGFR protein or specifically EGFRvIII have already entered, or are about to enter clinical evaluation, including peptide-based vaccines (44)(45)(46), chimeric antigen receptor (CAR) T cells (47,48), as well as anti-EGFR antibodybased approaches (22,49,50).…”

Section: Discussionmentioning

confidence: 99%

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Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors

Felsberg¹,

Hentschel²,

Kaulich³

et al. 2017

Clin Cancer Res

143

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors

Felsberg¹,

Hentschel²,

Kaulich³

et al. 2017

Clin Cancer Res

143

View full text Add to dashboard Cite

“…However, this common pathway could be regulated by numerous cellular events which generate different downstream phenotypes. For example, signaling crosstalk is possible between the VEGF pathway and epidermal growth factor receptor variant III (EGFRvIII), and this receptor variant is found to be a driver of glioblastoma aggressiveness by promoting invasion and angiogenesis via activation of Src pathways [28]. In comparison, the expression of EGFRvIII is not seen in meningiomas [29].…”

Section: Discussionmentioning

confidence: 99%

Application of arterial spin labeling perfusion MRI to differentiate benign from malignant intracranial meningiomas

Qiao

Kim

Wang

et al. 2017

European Journal of Radiology

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Purpose: Differentiating WHO grade I–III of meningioma by non-invasive imaging is challenging. This study investigated the potential of MR arterial spin labeling (ASL) to establish tumor grade in meningioma patients. Material and methods: Pseudo-continuous ASL with 3D background suppressed gradient and spin echo (GRASE) was acquired on 54 patients with newly diagnosed or recurrent intracranial meningioma. Perfusion patterns characterized in CBF color maps were independently evaluated by three neuroradiologists blinded to patient history, and correlated with tumor grade from histo-pathological review. Results: Three perfusion patterns could be discerned by visual evaluation of CBF maps. Pattern 1 consisted of homogeneous hyper-perfusion of the entire tumor; pattern 2 demonstrated heterogeneous hyper-perfusion; pattern 3 showed no substantial hyper-perfusion. Evaluation of the perfusion patterns was highly concordant among the three readers (Kendall W = 0.9458, P < 0.0001). Pattern 1 was associated with WHO Grade I meningioma of (P < 0.0001). Patterns 2 and 3 were predictive of WHO Grade II and III meningioma (P < 0.0001), with an odds ratio (OR, versus pattern 1) of 49.6 (P < 0.01) in a univariate analysis, and an OR of 186.4 (P < 0.01) in a multivariate analysis. Conclusion: Qualitative evaluation of ASL CBF maps can help differentiate benign (WHO Grade I) from higher grade (WHO Grade II and III) intracranial meningiomas, potentially impacting therapeutic strategy.

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“…EGFRvIII is expressed in GBM cell surface; therefore, CAR-T cell targeting EGFRvIII is a novel strategy worth studying [47]. Morgan et al conducted a series of experiments to construct competent CARs and evaluated the ability of CAR-engineered T cells recognizing EGFRvIII.…”

Section: Target Antigen Expressing On Solid Tumor Cell Surfacementioning

confidence: 99%

Chimeric antigen receptor T cells: a novel therapy for solid tumors

et al. 2017

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The chimeric antigen receptor T (CAR-T) cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs) expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2), and mesothelin (MSLN), as well as the challenges for CAR-T cell therapy.

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EGFRvIII mutations can emerge as late and heterogenous events in glioblastoma development and promote angiogenesis through Src activation

Cited by 84 publications

References 43 publications

Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors

Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors

Application of arterial spin labeling perfusion MRI to differentiate benign from malignant intracranial meningiomas

Chimeric antigen receptor T cells: a novel therapy for solid tumors

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