Overcoming Chemoresistance in Triple-negative Breast Cancer: New Strategies

Abstract

Triple-negative breast cancer (TNBC) remains a formidable challenge in oncology due to its aggressive nature, limited treatment options, and high propensity for chemoresistance, underscoring the urgent need for innovative therapeutic strategies. This review synthesizes current research to address the molecular mechanisms driving chemoresistance and explores emerging approaches to overcome this critical barrier in TNBC management. The review highlights key insights, including the roles of cancer stem cells (CSCs), dysregulated signaling pathways (e.g., PI3K/AKT, Wnt/β-catenin), and epigenetic modifications in fostering resistance. It examines advances in miRNA-based therapies, targeted inhibition of resistance-associated proteins (e.g., mixed lineage kinase 4 (MLK4), dual serine/threonine and tyrosine protein kinase (DSTYK)), and the potential of nanotechnology for precision drug delivery. Additionally, the discussion covers combination therapies, metabolic reprogramming, and immune modulation as promising strategies. The integration of these approaches aims to disrupt resistance mechanisms and improve therapeutic efficacy in TNBC. Future research should prioritize biomarker-driven patient stratification, clinical validation of preclinical findings, and the development of multitargeted regimens to address TNBC heterogeneity. Exploring the tumor microenvironment (TME) and leveraging multi-omics data will further refine personalized treatment paradigms. These efforts are essential to translate scientific discoveries into effective therapies and improve outcomes for TNBC patients.