Cediranib enhances control of wild type EGFR and EGFRvIII-expressing gliomas through potentiating temozolomide, but not through radiosensitization: implications for the clinic.

Publication/Presentation Date

11-1-2011

Abstract

Glioblastomas (GBM) frequently overexpress the epidermal growth factor receptor (wtEGFR) or its mutant, EGFRvIII, contributing to chemo- and radioresistance. The current standard of care is surgery followed by radiation therapy with concurrent temozolomide (TMZ) followed by adjuvant TMZ. New treatment strategies for GBM include blockade of EGFR signaling and angiogenesis. Cediranib is a highly potent receptor tyrosine kinase inhibitor that inhibits all three VEGF receptors. This study investigated the radiosensitizing potential of cediranib in combination with TMZ in U87 GBM xenografts expressing wtEGFR or EGFRvIII. U87 GBM cells stably transfected with either wtEGFR or EGFRvIII were injected into the hind limbs of nude mice. Cediranib was dosed at 3 mg/kg daily five times a week orally for 2 weeks. TMZ was dosed at 10 mg/kg once only on day 0. Radiotherapy (RT) consisted of 3 fractions of 5 Gy (days 0-2). Cediranib did not radiosensitize either tumor type; however, cediranib did enhance the effectiveness of TMZ in both transfectants. Our results suggest that combining cediranib with temozolomide in the clinic will lead to improved tumor control.

Volume

105

Issue

2

First Page

181

Last Page

190

ISSN

1573-7373

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

21516367

Department(s)

Administration and Leadership

Document Type

Article

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