Translational paradigm of Advanced Nanoscale Strategies for Triple Negative Breast Cancer (TNBC): Mechanistic Insights, Metastatic Pathways, and emerging theragnosis

Abstract

Triple-negative breast cancer (TNBC) represents one of the most aggressive forms of breast cancer, accounting for about one in five cases. Unlike other subtypes, TNBC lacks the key hormone receptors, estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2), that are typically targeted in treatment, leaving patients with limited therapeutic options. As a result, chemotherapy remains the mainstay of treatment, though its benefits are often short-lived. High relapse rates and poor long-term outcomes continue to pose major challenges in managing this disease. This review explores the genetic alterations frequently associated with TNBC, particularly mutations in BRCA1/2 and TP53, and highlights the profound heterogeneity within its tumor microenvironment. Distinct molecular pathways and metabolic dysregulations contribute to TNBC’s complexity, complicating effective treatment. To comprehend their pathobiology, cultured cells like MDA-MB-231 and MDA-MB-468 are frequently utilized in in vitro investigations. Conventional medicines are inadequate, whereas developing nanotechnology presents exciting opportunities. Nanotheranostics, nanoparticles engineered for simultaneous therapeutic and diagnostic applications, have exhibited significant promise in the management of TNBC. These nanocarriers enable targeted drug delivery, enhanced imaging, prolonged circulation, reduced toxicity, and protection against drug degradation. They are also employed in photodynamic treatment and real-time tumor imaging. This review provides a thorough and prompt synthesis of the molecular complexity of TNBC and underscores the revolutionary impact of nanomedicine, serving as a significant resource for researchers, clinicians, and innovators in precision oncology.