Clinical advances and challenges of antibody-mediated targeted drug delivery in breast cancer therapeutics

Breast cancer (BC) continues to present a universal health burden, and thus there is a need to develop antigen-targeted therapies with lower off-target toxicity and a greater therapeutic index. The antibody-mediated targeted drug delivery systems are especially antibody–drug conjugates (ADCs) and antibody-conjugated nanoparticles (ACNPs) have become the game changers in the age of precision oncology. By taking advantage of the selectivity of monoclonal antibodies, these platforms preferentially target tumor-associated antigens (TAAs) including HER2, TROP-2, HER3 and LIV-1, which avoids off-target toxicity and overcomes drug resistance. This review presents a detailed discussion of the principles of design, mechanisms and clinical advancements of ADCs and ACNPs in the treatment of BC. Major advances are in the field of advanced linker technology, site selective conjugation techniques, and novel payloads that have potent antitumor effects. A number of new-generation ADCs have demonstrated promising clinical results, especially in HER2-positive and triple-negative forms of the BC. Moreover, nanocarrier-based drug delivery systems like trastuzumab-functionalized liposomes or polymeric nanoparticles are more advantageous in drug loading and release, as well as tumor penetration. In spite of this progress there are still several challenges including heterogeneity of tumor antigens, immunogenicity and off-target toxicity which hinder clinical translation. Bispecific antibodies, dual-payload ADCs, and patient-specific antigen profiling are some of the strategies under research to improve the precision of therapeutic treatment. With the application of molecular targeting and drug delivery innovation, the biology of antibody-mediated systems has enormous potential to transform the standard of treatment of BC and pave the way to customised medicine. Antigen selection, rational linker-payload design, and biomarker-directed patient stratification. In BC, ADC-led antibody-mediated delivery is setting therapeutic delivery action, and after all, toxicity management and mitigation of resistance are core clinical factors in success.