Combination of phosphotidylinositol-3-kinase targeting with cetuximab and irradiation: A preclinical study on an orthotopic xenograft model of head and neck cancer.

Combination of phosphotidylinositol-3-kinase targeting with cetuximab and irradiation: A preclinical study on an orthotopic xenograft model of head and neck cancer.

Head Neck. 2016 Aug 10;

Authors: Bozec A, Ebran N, Radosevic-Robin N, Chamorey E, Yahia HB, Marcie S, Gautier M, Penault-Llorca F, Milano G

Abstract
BACKGROUND: The purpose of this study was to investigate the effects of combining the phosphotidylinositol-3-kinase (PI3K) inhibitor buparlisib (BKM)120 with the anti-epidermal growth factor receptor (EGFR) agent cetuximab and radiotherapy (RT) on an orthotopic model of head and neck squamous cell carcinoma (HNSCC).
METHODS: We evaluated the antitumor efficacy of BKM120, cetuximab, and RT, administered alone or in combination, using the human PIK3CA-mutated HNSCC cell line, CAL33, injected into the floor of the mouth of nude mice.
RESULTS: Compared with control, the BKM120-cetuximab and the BKM120-cetuximab-RT combinations led to the highest tumor inhibition (p < .001). The highest inhibitory effect of treatments on cell proliferation, mitogen-activated protein kinase (MAPK) and PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathways were found with the BKM120-cetuximab association. The association of BKM120 and cetuximab with RT inhibited RT-induced activation of the MAPK pathway.
CONCLUSION: These results can serve as a preclinical rationale for innovative treatments combining PI3K inhibition with anti-EGFR therapies and irradiation in patients with HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 27507562 [PubMed - as supplied by publisher]

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