Advances in targeted therapy for triple-negative breast cancer: a review of key antigens and recent advances

The most aggressive subtype of breast cancer is triple-negative breast cancer (TNBC), which affects about 10-15% of all breast cancer cases. TNBC is associated with a poor prognosis and drug resistance due to the lack of oestrogen, progesterone, and HER2 receptors. Developing targeted immunotherapy for TNBC was challenged by identifying TNBC-specific antigens that can be suitable targets for antibody and nanobody-based therapies. Evidence from cancer- targeted therapy demonstrates that treatment outcomes are more successful when the target antigen is either overexpressed in tumour tissue or exhibits tumour specificity. Several antigens have been overexpressed in TNBC, including programmed cell death protein 1 (PD-1), programmed death-ligand 1(PD-L1), mesothelin (MSLN), trophoblast cell-surface antigen 2 (Trop-2), tumour endothelial marker 8 (TEM8), etc. There have been investigations targeting these antigens with antibodies, nanobodies, small molecules, peptides, and miniproteins for targeted treatment of TNBC. Antibodies known as Aembrolizumab, Atezolizumab, and Sacituzumab Govitecan-hziy have been approved by the FDA, and many are under investigation. The present review discusses the antigens with high expression in TNBC, their role in cancer development and progression, and the targeted therapies like antibodies, recombinant proteins, and antibody-drug conjugates (ADC).