Dual blockade of PI3K and MEK in combination with radiation in head and neck cancer. (June 2018)

• Record Type: Journal Article
• Authors: Blas, Kevin; Wilson, Thomas G.; Tonlaar, Nathan; Galoforo, Sandra; Hana, Alaa; Marples, Brian; Wilson, George D.
• Is Part Of: Clinical and translational radiation oncology. Volume 11(2018)
• Page Start: 1
• Page End: 10
• Publication Date: 2018-06
• Subjects: Head and neck cancer -- Radiation -- Targeted agents -- Xenografts -- Growth delay; Cancer -- Radiotherapy -- Periodicals; Oncology -- Periodicals; Cancer -- Radiotherapy; Oncology; Radiation Oncology; Neoplasms -- radiotherapy; Translational Medical Research; Periodicals; Electronic journals; Periodicals; 616.9940642
• DOI: 10.1016/j.ctro.2018.04.003
• Languages: English
• ISSNs: 2405-6308

Abstract

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.