Modern Models of Breast Cancer: Integration of Molecular Biological Approaches for Study of Signaling Pathways and Development of Therapies

Abstract Breast cancer (BC) is one of the most common and lethal cancers in women. The low predictive value of conventional preclinical models necessitates the creation of more relevant experimental systems. The review presents a comprehensive analysis of the evolution of BC models from simple 2D cultures to complex 3D systems and in vivo models. Key platforms are discussed, including 3D spheroids, patient-derived organoids (PDOs), and organ-on-a-chip technologies. Special attention is given to modern in vivo models, including patient-derived xenografts (PDXs), patient-derived orthotopic xenografts (PDOXs), and humanized mice for studying immunotherapy. Personalized models (PDOs and PDXs), which preserve the heterogeneity of the original tumor, are becoming the gold standard for preclinical screening and the development of individualized therapy. The review details the roles of key cell signaling receptors (ER and HER2) and the PI3K/AKT/mTOR signaling pathway in BC carcinogenesis, as well as the mechanisms of drug resistance. Advanced molecular technologies (CRISPR/Cas9, next-generation sequencing, and multi-omics analyses) are shown to play a crucial role in studying tumor biology and searching for new therapeutic targets. The integration of complex model systems with modern analytical platforms paves the way for personalized oncology and improved clinical outcomes in BC.