Multifaceted interactions between lncRNA-associated ceRNA networks and small molecules in triple-negative breast...

Triple Negative Breast Cancer (TNBC) is the most aggressive subtype of breast cancer, marked by intrinsic and acquired chemoresistance and a lack of response to endocrine therapy and chemotherapy. This necessitates the development of novel, safe, and cost-effective treatment strategies. Recent advances include small molecules, drug repositioning, dual-targeting agents, combinatorial therapies, and splicing inhibitors. Comprehensive molecular profiling, including transcriptomic comparisons between primary and secondary tumors, is crucial for identifying chemoresistance mechanisms and revealing therapeutic vulnerabilities. ceRNA networks (lncRNA-miRNA-mRNA) provide insights into tumorigenesis and progression, facilitating the identification of subtype-specific biomarkers in the heterogeneous landscape of TNBC. lncRNAs, with their complex structure and tissue-specific expression, are promising both as biomarkers and therapeutic targets. Liquid biopsies and next-generation sequencing are paving the way for personalized lncRNA-based treatments by enabling real-time monitoring of tumor heterogeneity and therapeutic response. While miRNA-mRNA interactions have been extensively studied, the involvement of lncRNA within the ceRNA network remains poorly understood. Elucidating these interactions and their modulation by small molecules may lead to more effective, personalized treatment strategies for TNBC. This review examines long non-coding RNA (lncRNA)- associated competing endogenous RNA (ceRNA) networks, their therapeutic potential, and their application as predictive biomarkers in triple-negative breast cancer (TNBC).