Dacomitinib and gedatolisib in combination with fractionated radiation in head and neck cancer.

Document Type

Article

Publication Date

11-8-2020

Publication Title

Clinical and translational radiation oncology

Abstract

Background and purpose: There has been little success targeting individual genes in combination with radiation in head and neck cancer. In this study we investigated whether targeting two key pathways simultaneously might be more effective.

Materials and methods: We studied the effect of combining dacomitinib (pan-HER, irreversible inhibitor) and gedatolisib (dual PI3K/MTOR inhibitor) with radiation in well characterized, low passage xenograft models of HNSCC in vitro and

Results: Dacomitinib showed differential growth inhibition in vitro that correlated to EGFR expression whilst gedatolisib was effective in both cell lines. Neither agent radiosensitized the cell lines in vitro. In vivo studies demonstrated that dacomitinib was an effective agent alone and in combination with radiation whilst the addition of gedatolisib did not enhance the effect of these two modalities despite inhibiting phosphorylation of key genes in the PI3K/MTOR pathway.

Conclusions: Our results showed that combining two drugs with radiation provided no added benefit compared to the single most active drug. Dacomitinib deserves more investigation as a radiation sensitizing agent in HNSCC.

Volume

26

First Page

15

Last Page

23

DOI

10.1016/j.ctro.2020.11.003

ISSN

2405-6308

PubMed ID

33251343

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