Abstract 4211: The proteomic characterization of HNSCC patient-derived xenografts

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the US and a leading cancer worldwide. There has been little change in the prognosis for these patients despite extensive research and FDA approval of the targeted therapy cetuximab. Cetuximab has been effective in immortalized HNSCC cell lines but demonstrates only a modest benefit for a subset of patients. This gap between pre-clinical discovery and testing and final clinical efficacy can be narrowed improving the translational relevance of preclinical model systems. Patient derived xenografts (PDXs) have emerged as a promising approach in several cancers. We sought to define and compare the protein expression patterns between primary HNSCC and PDXs derived from 13 patient tumors and test predictive biomarkers to cetuximab therapy. We compared 13 PDXs propagated at the University of Pittsburgh and analyzed for the expression levels of 190 proteins by reverse-phase protein array (RPPA) to 212 HNSCC specimens and 4566 cancer specimens from TCGA also analyzed by RPPA. We found that 12/13 PDXs were more like HNSCC than any of 14 other cancer types analyzed. Unsupervised clustering of the primary HNSCC and the PDXs demonstrated that PDXs clustered together, indicating some differences in protein expression between HNSCC and PDXs. Further analysis demonstrated that a subset of the proteins were different between the mouse derived PDXs and the primary HNSCC while a second subset were similar between mouse derived PDXs and primary HNSCC. Proteins that were different between these two groups may be poor candidates for translational models, but proteins that were similar may prove useful. We tested the different responses to cetuximab using the PDXs. We found that a PDX with high EGFR/pEGFR expression was more sensitive to cetuximab treatment than a PDX with low EGFR/pEGFR expression. These results suggest that improved model systems used for translational may predict clinical responses. RPPA measurement of protein expression in PDXs and primary cancers demonstrates that PDXs do represent HNSCC overall. Comparison of the PDXs specifically with primary HNSCC reveals that PDXs are not an appropriate model system for all targeted therapies/studies but provide an effective model for many studies of interest in the field. Citation Format: Hua Li, Sarah E. Wheeler, Yongseok Park, Zhenlin Ju, Ann Marie Egloff, Michele Fichera, Sufi Thomas, Gordon B. Mills, Jennifer R. Grandis. The proteomic characterization of HNSCC patient-derived xenografts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4211. doi:10.1158/1538-7445.AM2015-4211