Abstract 2170: Single mouse preclinical trial: A tool for translational research
| Autor: | C Mignard, M Hillairet de boisferon, F Bichat, D France, O Duchamp |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Cancer Research. 78:2170-2170 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Roughly, 85% of preclinical agents entering oncology clinical trials fail to demonstrate sufficient safety or efficacy to gain regulatory approval. Hence, there is a need for experimental systems which better mimic the inter-patient response heterogeneity observed in the clinic. Patient-derived tumor xenograft (PDX) mouse models have emerged as a relevant oncology research tool to study tumor evolution, drug response, biomarkers, resistance phenomenon and adjusting chemotherapeutic approaches for individual patients. We will here expose the effectiveness of the single mouse preclinical trial paradigm for evaluating drug response, as mono or combo therapy using our well-characterized PDX collection. Based on the “1 PDX tumor/1 mouse/1 treatment” experimental design, a cohort of colorectal, breast, pancreas, lungs PDX models (minimum 20 of each) was used to explore response to Standard Of Care (SOC) and combo therapy used in clinic. We compared single-animal response data with treatment group data taken from historical experiments. We demonstrated that about >80% of the individual response matched the treatment group data, supporting the idea of using one single animal to predict the drug response. The response of each PDX to treatment was correlated to their histological and genetic profiles. This approach represents a new experimental design to address the tumor biology of cancer patients, and investigate targeted therapies in relevant mouse models, which could improve our ability to predict clinical trial responses, stratify patients for clinical trial, identify drug resistance mechanism, responsive sub-populations as well as biomarker. By combining genomic profiling data and drug screening data, and clinical data from patients, SMPT process is a helpful tool for precision cancer medicine and individualized drug selection. Citation Format: C Mignard, M Hillairet de boisferon, F Bichat, D France, O Duchamp. Single mouse preclinical trial: A tool for translational research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2170. |
| Databáze: | OpenAIRE |
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