Epigenetic Therapeutics: Reprogramming Triple-Negative Breast Cancer into Responsive Subtypes

Triple negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging subtypes of breast cancer due to its lack of targeted treatment options and high plasticity. Increasing evidence suggests that epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA regulation, play a pivotal role in facilitating TNBC phenotype by influencing the expression of genes involved in subtype reprogramming. Modulating these epigenetic marks offers a promising strategy to drive TNBC subtype conversion toward less aggressive forms that are more responsive to treatment, thereby enhancing the therapeutic efficacy. By targeting enzymes such as DNA methyltransferases and histone modifiers using epigenetic drugs (epidrugs), TNBC cells can be resensitized to hormone therapy, chemotherapy, and targeted treatments. This review delves into the role of epigenetic modulation in harnessing the plasticity of TNBC to drive its conversion into subtypes with better prognoses and discusses problems and limitations associated with the use of epidrugs in this context. By promoting subtype conversion, epidrugs offer a promising strategy for providing more personalized and effective therapies for TNBC patients.