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

Abstract

Background and purpose: 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. Materials and methods: 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. Results: 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. Conclusions: No significant benefit was gained by the combined use of the two agents with RT even though each was efficacious when used alone. Keywords: Head and neck cancer, Radiation, Targeted agents, Xenografts, Growth delay