Abstract 1367: Characterization of spontaneous metastases in Champions TumorGraft™ models

Abstract

Abstract Oncology drug development is challenged by an absence of model systems that accurately mimic the full metastatic processes during disease progression. Methods for establishing metastases generally involve orthotopic implantation or intravenous delivery of cell line-based xenografts. These cell line-based models can capture the seeding phase of the metastatic process but do not address the processes involved in remodeling of the extracellular matrix to allow for invasion into nearby tissues or dissemination to distance sites throughout the body via the lymphatic or the circulatory system. Extensive characterization of Champions TumorGraft™ models demonstrates that spontaneous metastasis in our platform may not be a rare event as it has been verified in 8 different models and preliminary data indicates multiple additional occurrences. Further, the capacity for spontaneous metastasis is not indication specific as it has been observed in Champions TumorGrafts derived from patients with multiple cancer types (e.g. ovarian, breast, H&N, and lung). The development and incidence rate of TumorGraft metastasis seems to correlate with the aggressiveness of disease and occurrence of metastases in the patient. For example, 83% of mice implanted with Champions TumorGraft breast cancer model CTG-0033 develop liver and/or spleen metastases. This Champions TumorGraft was derived from a patient with aggressive disease that failed to respond to first and second line treatments, and developed metastases in multiple organs including the liver. In this report, growth rates, metastases formation and molecular characterization in primary subcutaneous Champions TumorGraft models were compared with their corresponding metastatic lesions to identify changes that may correlate with the formation of metastases. Overall, this study further demonstrates that Champions Oncology TumorGraft platform preserves the biological properties of the original human tumor including spontaneous metastatic behavior and is therefore ideal for oncology drug development programs focused on the inhibition of metastases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1367. doi:1538-7445.AM2012-1367