Dual blockade of PI3K and MEK in combination with radiation in head and neck cancer

Clinical and Translational Radiation Oncology
Kevin BlasGeorge D Wilson

Abstract

In this study we have combined fractionated radiation treatment (RT) with two molecular targeted agents active against key deregulated signaling pathways in head and neck cancer. We used two molecularly characterized, low passage HNSCC cell lines of differing biological characteristics to study the effects of binimetinib and buparlisib in combination with radiation in vitro and in vivo. Buparlisib was active against both cell lines in vitro whereas binimetinib was more toxic to UT-SCC-14. Neither agent modified radiation sensitivity in vitro. Buparlisib significantly inhibited growth of UT-SSC-15 alone or in combination with RT but was ineffective in UT-SCC-14. Binimetinib did cause a significant delay with RT in UT-SCC-14 and it significantly reduced growth of the UT-SCC-15 tumors both alone and with RT. The tri-modality treatment was not as effective as RT with a single effective agent. No significant benefit was gained by the combined use of the two agents with RT even though each was efficacious when used alone.

Citations

Sep 10, 2020·Frontiers in Oncology·Katharina HintelmannThorsten Rieckmann
Dec 1, 2020·Clinical and Translational Radiation Oncology·George D WilsonSandra Galoforo
Feb 18, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Michelle J LeeDaniel E Johnson
Mar 24, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Niluja ThiruthaneeswaranCatharine West

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Methods Mentioned

BETA
X-ray
xenografts
xenograft

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