Hsp90 inhibition enhances PI-3 kinase inhibition and radiosensitivity in glioblastoma.

Purpose: Combined targeting with a PI3-kinase inhibitor, BKM120, and an Hsp90 inhibitor, HSP990, was investigated as a multi-targeted approach to potentiate cell death in glioblastoma (GBM). Additionally, the effect of dual drug treatment combined with cytotoxic stress (radiation therapy) was examined.

Methods: Four human GBM cell lines containing wild-type or mutated PTEN and/or p53 were studied.

Epidermal growth factor receptor mutation status and rad51 determine the response of glioblastoma to multimodality therapy with cetuximab, temozolomide, and radiation.

Purpose: EGFR amplification and mutation (i.e., EGFRvIII) are found in 40% of primary GBM tumors and are believed to contribute to tumor development and therapeutic resistance.

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

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.

Epidermal growth factor receptor expression modulates antitumor efficacy of vandetanib or cediranib combined with radiotherapy in human glioblastoma xenografts.

Purpose: The purpose of this study was to determine the ability of radiation therapy (RT) combined with the tyrosine kinase inhibitors (TKI) vandetanib (antiepidermal growth factor receptor [EGFR] plus antivascular endothelial growth factor receptor [anti-VEGFR]) and cediranib (anti-VEGFR) to inhibit glioblastoma multiforme (GBM) growth. A secondary aim was to investigate how this regimen is modulated by tumor EGFR expression.

Methods And Materials: Radiosensitivity was assessed by clonogenic cell survival assay.

Investigation of acoustic radiation force for radio-protecting normal tissues during radiation therapy.

Radiation therapy (radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to erradicate malignant cells. Normal tissue tolerance is currently a major dose-limiting factor. As molecular oxygen plays a critical role in creating the radiation damage, we propose a novel approach, that is, the use of acoustic radiation force (ARF) to suppress the normal tissue oxygenation, for the purpose of protecting the normal tissue and increasing its tolerance during radiotherapy.