Targeted biologics for TNBC: Advances in nanobodies, antibodies, peptides, and aptamers

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. This molecular profile limits responsiveness to hormonal or targeted therapies, often with poor outcomes and high recurrence. TNBC's heterogeneity subtypes, along with features such as high tumor mutational burden and immunosuppressive tumor microenvironment, underscore the urgent need for innovative approaches. This review explores translational advances in molecular therapies, focusing on conventional antibodies, nanobodies, peptides, and aptamers to target key TNBC molecules. Conventional antibody-based modalities, including antibody-drug conjugates (e.g., sacituzumab govitecan against TROP2) and checkpoint inhibitors (e.g., atezolizumab for programmed death-ligand 1 [PD-L1]), leverage antibody-dependent cellular cytotoxicity, direct antigen blockade, and immune activation to combat tumor growth and evasion. Nanobodies, prized for their compact size and stability, facilitate enhanced tumor penetration in applications and diagnostic imaging. Peptides, such as cell-penetrating variants and vaccines (e.g., HER2-derived AE37), disrupt oncogenic pathways, enable precise drug delivery via conjugates, and elicit antigen-specific immune responses. Aptamers provide high-affinity binding to antigens like nucleolin (e.g., AS1411), supporting targeted delivery and tumor microenvironment modulation. Together, these platforms hold strong potential to overcome chemoresistance, enable subtype-specific treatment personalization, and improve outcomes through synergistic combinations, advancing precision oncology in TNBC.