Abstract 1223: Establishment, characterization and evaluation of a panel of head and neck patient-derived xenograft (PDX) models

Abstract

Abstract Background: Head and neck cancers account for over five hundred thousand cases worldwide each year. Primary risk factors include tobacco use, alcohol consumption, human papillomavirus (HPV) infection, and Epstein-Barr virus (EBV) infection with certain cancer subtypes disproportionally affecting minorities. Standard treatment for these cancers consists of surgical tumor debulking followed by a platinum-based agent alone or in combination with an EGFR-targeting therapy when relevant. The rate of initial response to treatment is high; however, the majority of patients develop recurrent disease resistant to most secondary chemotherapy treatments, demonstrating the need for identifying additional useful therapies. To better understand pathways involved in head and neck cancers and identify useful novel therapies for this disease, we have established a panel of low passage, patient-derived xenograft (PDX) models representing head and neck cancers and characterized them by activating mutation analysis and receptor expression. Panel drug screening studies were also performed comparing platinum regimens and select targeted therapies and correlating with clinical outcome. Methods: START-PDX head and neck models were established in immune-deficient mice from primary or metastatic patient tissue and once established were confirmed by histologic comparative analysis and linked with patient treatment and outcome data. For each model DNA was extracted and subjected to exon sequencing of known oncogenes and growth factor receptor densities were interrogated using immunohistochemistry. Drug sensitivity studies were performed evaluating models towards chemotherapy and targeted agents. Study endpoints included tumor volume and time from treatment initiation with tumor growth inhibition, delay and regression reported at study completion. Results: To date we have established and validated twenty-five head and neck low passage START-PDX models. High EGFR staining (3+) was reported in over 70% of these models but only 10% reported HER2 and HER3 staining. Activity of platinum regimens was marked and correlated with clinical outcome with over 75% concordance. High EGFR expression did not correlate to cetuximab sensitivity even in models with wildtype K-Ras. However, models found sensitive to erlotinib also demonstrated sensitivity to cetuximab. Conclusion: We have established a panel START-PDX head and neck models and characterized mutation status, receptor expression and benchmarked sensitivity of platinum and select targeted therapies. This panel can be utilized as a valuable screening tool in early and late-stage biomarker discovery and oncology drug development. Citation Format: Michael J. Wick, Teresa Vaught, Lizette Gamez, Armando Diaz, Justin Meade, Monica Farley, Alyssa Moriarty, Jennifer Carlile, Anthony Tolcher, Drew Rasco, Amita Patnaik, Richard Newman, Kyriakos Papadopoulos. Establishment, characterization and evaluation of a panel of head and neck patient-derived xenograft (PDX) models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1223. doi:10.1158/1538-7445.AM2014-1223