Abstract 1289: A preclinical platform of PDX breast cancer models and their cellular counterparts to identify resistance mechanisms and novel therapeutic options

Abstract Despite significant advancements in understanding the biology and genetics of breast cancer, the development of effective therapies requires predictive and physiologically relevant preclinical models for their evaluation. In this context, patient-derived xenografts (PDX) have become a standard tool as they reproduce the biology of the original tumors in terms of histology, genotype, and response to chemotherapy. They have proven their relevance in studying pathways leading to cancer development and progression, mechanisms related to tumor resistance, and identifying new effective therapies. We offer a preclinical platform of over 60 fully characterized breast cancer PDX models and their in vitro cell derivatives for preclinical evaluation of new treatment modalities. Our platform consists of a PDX collection of 43 TNBC models, 9 ER+, 5 HER2+, 3 Luminal B (ER+ HER2+) models, and 14 cellular models derived from a subset of these PDX (PDXDC), representing the diversity of breast cancer. PDX models were obtained by transplanting post-operative tumor samples, either by grafting tumor fragments into the interscapular region of nude mice or by injecting dissociated tumor cells into the mammary fat pad of NOD-Scid mice. PDXDC were obtained from dissociated PDX tumors cultured under various media and matrix conditions. All models (PDX and PDXDC) were characterized at molecular level, including transcriptomic, whole exome sequencing, IHC marker staining and/or cytometry analysis. PDX were characterized pharmacologically for response to standards of care as a single agent or in combination. Our PDX and PDXDC panels primarily reflects the molecular heterogeneity of breast cancer and accurately reproduces the molecular and drug response profile of patient tumors. It is widely used for standard drug evaluations, but also for in vivo "mouse clinical trials" (MCT) which provide more predictive preclinical data on the efficacy of a single agent or drug combination. Additionally, we generated standard-of-care resistant models from our PDX panel to study the resistance mechanisms underlying breast cancer progression and to mimic what is observed in the clinic. Associated to in vitro cell derivatives, our collection provides a powerful preclinical platform for translational and preclinical research to identify mechanisms underlying acquired resistance to current therapies and develop novel treatment strategies against breast Cancers. Citation Format: Emilie Indersie, Léa Sinayen, Aurore Gorse, Marie Tavernier, Enora Le Ven, Ester Morgado, Laurent Pouyet, François Romagné, Olivier Déas. A preclinical platform of PDX breast cancer models and their cellular counterparts to identify resistance mechanisms and novel therapeutic options [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 1289.