Advanced strategies for targeting severe triple-negative breast cancer

Triple-negative breast cancer is the most aggressive breast cancer subtype, defined by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Despite recent achievements in cancer management, triple-negative breast cancer (TNBC) remains clinically challenging due to its unique molecular heterogeneity, absence of targeted therapy, and poor prognosis. This chapter provides a detailed overview of the most advanced strategies to target TNBC. In this regard, the molecular landscape of TNBC is discussed, and key genetic and molecular alterations associated with its aggressiveness and anti-treatment resistance are described. At the same time, the existing standard of care for this malignancy is reviewed, and the limitations of current approaches are discovered. As it is central to the chapter, the advanced methods of attacking TNBC are analyzed, including immunotherapies, as well as novel targeted therapies and combination approaches. The mechanisms of action are provided, and preclinical and clinical evidence in this field is studied. Besides, the promising approaches for patient stratification through biomarkers are evaluated. Numerous clinical trials are described, and the authors conclude based on the results available. Finally, the future directions of TNBC research are discussed, and, in particular, the role of cytotoxic drugs and advanced nanotechnology in the development of novel drug delivery systems, promising horizons of synthetic lethality approaches, and translation of multi-omics references into personalized treatment of patients with TNBC. Key challenges and peculiarities of the current therapy development defined based on the knowledge available are analyzed, such as the role of selective stratification and well-developed biomarkers in trial design, as well as the necessity to understand the peculiarities of the tumor microenvironment and tumor evolution.