Exploring the Molecular and Genomic Landscape of the Dark Agouti Rat Mammary Adenocarcinoma: Preliminary Insights for Triple-Negative Breast Cancer Modeling.

Abstract

The isogenic, tumor-bearing Dark Agouti Mammary Adenocarcinoma (DAMA) model is commonly utilized in breast cancer research to evaluate mechanisms of, and interventions for chemotherapy-induced toxicity and tumor response. However, the biological subtype, immune landscape, and genomic profile of DAMA have remained uncharacterized. In this study, we comprehensively evaluated DAMA tumors naïve and exposed to methotrexate, assessing their histopathological, molecular, and genomic features. Our findings reveal that the DAMA model presents a platform to model the human triple-negative breast cancer (TNBC), as it exhibits substantial macrophage infiltration, the tumors display dysregulation of oncogenes Bcl2, Egfr, and potentially Myc, suggesting apoptotic resistance as a key mechanism driving growth. These characteristics position the DAMA model as a potential preclinical model for investigating TNBC biology, therapeutic responses, and drug toxicity.