Abstract 6494: Genetically characterized canine tumoral cell lines are relevant models to test the efficacy of new targeted therapies: Example of anti-MDM2 targeted therapy

Abstract Genetic characterization of cell lines is essential for understanding and predicting sensitivity to anti-tumoral targeted therapies. This study develops a panel of genetically characterized tumoral cell lines to test novel and repositioned anti-tumor therapies, focusing on canine mucosal melanoma (MM) and histiocytic sarcoma (HS) models. We established a diverse panel of MM and HS canine cell lines, leveraging the strong genetic and clinical similarities between canine and human cancers. Using long-read sequencing (Nanopore) technology, we performed comprehensive genetic characterization, identifying single nucleotide variants, structural variations, and copy number alterations. RNA sequencing complemented our genomic analysis by assessing gene expression profiles and potential fusion transcripts. Our methodology involved several key steps:1. Cell line establishment from tumor samples2. Comprehensive genetic profiling3. In vitro drug sensitivity screening4. In vivo validation through mouse xenograft modelsAs a proof of concept, we evaluated Idasanutlin, an MDM2 inhibitor, across our developed cell lines. Our findings demonstrated a clear correlation between TP53 status and drug sensitivity: cell lines with wild-type TP53 were sensitive to the drug, while those with mutated TP53 showed resistance. This result underscores the potential of genetic profiling to guide treatment decisions. The unique value of our approach lies in its ability to:· Identify biomarkers of drug response· Elucidate resistance mechanisms · Discover treatment-responsive subgroups based on genetic profile in previously untreated cancer· Inform the potential of new or repositioned targeted therapiesCanine cancer models offer distinct advantages, including:· Higher incidence of rare cancers in specific breeds· Genetic predispositions from selective breeding· Closer genetic and clinical similarity to human cancersOur cell line panel provides a systematic approach to validate therapeutic strategies tailored to specific genetic contexts. By integrating genomic, transcriptomic, and drug sensitivity data, we create a powerful research tool for both veterinary and human oncology. The research demonstrates the potential of comparative oncology in advancing cancer treatment. Our genetically characterized cell lines offer a comprehensive platform for drug screening and biomarker discovery, ultimately aiming to improve patient care and survival rates for challenging cancers. This work represents a significant step towards more personalized and precise cancer therapies, bridging the gap between preclinical research and clinical application. Citation Format: Pierre Montagne, Ulrich Jarry, Caroline Confais, Edouard Cadieu, Aline Primot, Nicolaï Hoffman, Armel Houël, Rémy Le Guével, Thomas Derrien, Catherine André, Jérome Abadie, Christophe Drieu La Rochelle, Benoit Hédan. Genetically characterized canine tumoral cell lines are relevant models to test the efficacy of new targeted therapies: Example of anti-MDM2 targeted therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6494.