Inhibition of MEK confers hypersensitivity to X‐radiation in the context of BRAF mutation in a model of childhood astrocytoma

Inhibition of MEK confers hypersensitivity to X‐radiation in the context of BRAF mutation in a model of childhood astrocytoma

Studebaker, A. Pediatric Blood and Cancer (2015) (Link to abstract)


This study explores the use of a MEK inhibitor in combination with ionizing radiation (XRT) in a model of BRAF- mutant anaplastic astrocytoma. The effect of MEK inhibition (selumetinib), XRT or the combination of both was evaluated in subcutaneous BRAF mutant xenografts. Inhibition of MEK signaling in BRAF mutant cells or in xenografts lead to complete suppression of FANCD2 and conferred hypersensitivity to XRT in BRAF mutant xenografts without increasing local skin toxicity.


*In the context of mutant BRAF in recurrent gliomas of childhood or anaplastic astrocytoma there is a possibility of potentiating XRT effects selectively in tumour cells by using MEK inhibition. This may allow reduced dosing of XRT and consequently reduced late effects.


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