Abstract 2798: Champions TumorGraft™ models represent oncology clinical trial populations.

Cancer Research(2014)

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摘要
One of the challenges in oncology drug development is the inability of traditional in vivo models to predict clinical responses. Champions Oncology overcomes this challenge through the use of its innovative Champions TumorGraft™ platform, where primary human tumors are implanted into immunocompromised mice in a manner that preserves the biological properties of the original human tumor. The current study evaluated the molecular and demographic characteristics of the Champions TumorGraft™ bank to demonstrate that these models closely resemble cancer patients that pharmaceutical companies encounter in clinical trials during the development of innovative and targeted oncology compounds. In particular, the relative frequency of ethnicity, age, and geographic location in the Champions TumorGraft™ bank closely aligns with patients enrolled in oncology clinical trials. For instance, greater than half of the models in Champions TumorGraft bank are derived from patients with advanced disease, who failed several previous lines of therapy. This is extremely important for accurate translational research, as most patients enrolling in critical mid-stage oncology clinical trials often have advanced disease and have failed multiple lines of therapy. Additionally, in recent years, clinical trials have progressed to designs where there are specific enrichments in patient populations/sub-populations based on the incorporation of companion diagnostics. Molecular evaluation of the Champions TumorGraft™ bank identifies models that possess genomic signatures or pathway expressions which can be used to identify and validate potential enrichment strategies. For example, 40% of Champions’ NSCLC models possess p53 mutations and 36% of all NSCLC clinical cases also possess p53 mutations according to the COSMIC database. Additionally, 50% of Champions colorectal TumorGraft models possess K-ras mutations, whereas 36% the clinical colorectal cancer population possesses this mutation. These cases, as well as other mutations observed across several tumor types, demonstrate that the TumorGraft mutation prevalence is representative of the prevalence in cancer patients. Together, these results demonstrate that Champions TumorGraft™ models represent a unique preclinical in vivo platform that correlate to oncology clinical trial populations. Overall, these results suggest that Champions TumorGraft™ models are capable of predicting the clinical effectiveness of drug candidates and can accelerate and enhance oncology drug development. Citation Format: Tin Oo Khor, Jay Friedman, Dhanrajan Tiruchinapalli, Nathan Anderson, David Sidransky, Elizabeth M. Bruckheimer. Champions TumorGraft™ models represent oncology clinical trial populations. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2798. doi:10.1158/1538-7445.AM2013-2798
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