Molecular Mechanisms of Mammary Carcinogenesis: Current Understanding and Prospects for Targeted Therapy

Abstract

Breast cancer (BC) is the leading oncologic disease among women worldwide: in 2022, approximately 2.3 million new cases and 670,000 deaths were reported. The disease’s molecular heterogeneity — the presence of luminal, HER2-amplified, and triple-negative subtypes — underlies the complexity of therapeutic approaches. This review synthesizes current data on oncogenic signaling pathways (PI3K/AKT/mTOR, RAS/MAPK, NOTCH, Wnt/β-catenin), epigenetic disturbances, and mechanisms of drug resistance in BC. Particular emphasis is placed on the evidence base for targeted drugs approved between 2018 and 2025: CDK4/6 inhibitors, PI3K/AKT pathway antagonists, antibody–drug conjugates (T-DXd, sacituzumab govitecan), PARP inhibitors, and immune checkpoint inhibitors. Based on an analysis of 31 high-level evidence sources (PubMed, Scopus, WoS), prospects for personalized oncology and overcoming resistance are discussed. The search for scientific publications was conducted in the following databases: PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. The following search queries in English were used: ‘breast cancer molecular mechanisms carcinogenesis», «breast cancer targeted therapy», «HER2 CDK4/6 inhibitors breast cancer», «triple-negative breast cancer immunotherapy PARP inhibitors», «antibody-drug conjugates breast cancer trastuzumab deruxtecan», and ‘PI3K/AKT/mTOR breast cancer». The search was conducted without language restrictions, with preference given to publications in English and Russian. Additional searches were conducted using the reference lists of selected articles.