Evaluating imaging biomarkers of acquired resistance to targeted EGFR therapy in xenograft models of human head and neck squamous cell carcinoma

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Abstract

Background: Overexpression of EGFR is a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). Patients with HNSCC who respond to EGFR-targeted tyrosine kinase inhibitors (TKIs) eventually develop acquired resistance. Strategies to identify HNSCC patients likely to benefit from EGFR-targeted therapies, together with biomarkers of treatment response, would have clinical value. Methods: Functional MRI and 18F-FDG PET were used to visualize and quantify imaging biomarkers associated with drug response within size-matched EGFR TKI-resistant CAL 27 (CALR) and sensitive (CALS) HNSCC xenografts in vivo, and pathological correlates sought. Results: Intrinsic susceptibility, oxygen-enhanced and dynamic contrast-enhanced MRI revealed significantly slower baseline R2*, lower hyperoxia-induced ΔR2* and volume transfer constant Ktrans in the CALR tumors which were associated with significantly lower Hoechst 33342 uptake and greater pimonidazole-adduct formation. There was no difference in oxygen-induced ΔR1 or water diffusivity between the CALR and CALS xenografts. PET revealed significantly higher relative uptake of 18F-FDG in the CALR cohort, which was associated with significantly greater Glut-1 expression. Conclusions: CALR xenografts established from HNSCC cells resistant to EGFR TKIs are more hypoxic, poorly perfused and glycolytic than sensitive CALS tumors. MRI combined with PET can be used to non-invasively assess HNSCC response/resistance to EGFR inhibition.

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Baker, L. C. J., Sikka, A., Price, J. M., Boult, J. K. R., Lepicard, E. Y., Box, G., … Robinson, S. P. (2018). Evaluating imaging biomarkers of acquired resistance to targeted EGFR therapy in xenograft models of human head and neck squamous cell carcinoma. Frontiers in Oncology, 8(JUL). https://doi.org/10.3389/fonc.2018.00271

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