Abstract LB362: Systematic development and characterization of orthotopic animal tumor models: A proactive approach to mimic patients' tumor microenvironments for drug discovery

Abstract Preclinical in vivo tumor models are crucial in translational research and the pharmaceutical industry, particularly for evaluating novel anti-cancer agents. While animal tumor models are widely used in both drug development and academic research, the majority of investigations have relied on subcutaneous (SC) transplantable tumor models. These models often fail to consider the orthotopic organ origin or the unique microenvironmental differences, leading to significant limitations. Despite many publications highlighting the advantages of orthotopic tumor models (ORTH) over SC models, there is a lack of systematic analysis and comparative characterization of these formats. In this study, we have systematically developed a comprehensive ORTH tumor model platform comprising over 80 orthotopic tumor models and covering more than 25 tumor types. ORTH tumor models have been enhanced for non-invasive monitoring and increased sensitivity of tumor growth and metastasis detection through labeling with multimodality imaging markers such as GFP, RFP, and bioluminescence or imaging with micro-CT or ultrasound. We optimized and streamlined technical procedures, throughput, and reproducibility of ORTH model development, facilitating the use of these models to assess anticancer agents in a large-scale format. To mimic the clinical situation, our characterization of these models includes growth profiles, metastatic features, and survival status. Additionally, ORTH models were compared with SC models regarding the efficacy of standard-of-care (SOC) drugs through side-by-side comparison studies. As expected, inconsistent responses to SOC therapeutics were observed in some models when comparing ORTH versus SC tumors. For models yielding inconsistent results, molecular analysis and model selection recommendations will be discussed. To date, this is the first study describing the generation of a considerably large orthotopic tumor model collection and conducting a comprehensive side-by-side characterization of ORTH and SC models. This proactive approach aims to improve the mimicry of patients' tumor microenvironments and enhance the clinical relevance and potentially increase the efficiency of translational research processes. Citation Format: WenQing Yang, Xusheng Yuan, Guangliang Yang, Xiaojun Tong, Weiqun Ding, Qiuxia Zhang, Feng Lu, Zhijian Yang. Systematic development and characterization of orthotopic animal tumor models: A proactive approach to mimic patients' tumor microenvironments for drug discovery abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr LB362.