Antibody-drug conjugate review in breast cancer: A targeted approach

Antibody-drug conjugates (ADCs) provide specificity for cytotoxic drugs as well as monoclonal antibodies (mAbs) and represent an important step in the treatment of breast cancer. This review summarizes the current status, efficacy, safety, and future prospects of ADCs in the treatment of breast cancer. mAbs enable drug delivery by detecting specific antigens on cancer cells. Cytotoxic payloads cause cell death upon internalization. The linker binds the mAb to the payload and influences drug release. All three components together form an ADC. Transtuzumab Emtansine 1 (T-DM1) (Kadcyla) targets human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has shown activity against both metastatic and early disease. Fam-trastuzumab deruxtecan (T-DXd; Enhertu) has shown improved progression-free survival and overall survival for T-DM1 in HER2-positive metastatic breast cancer. Sacituzumab govitecan (SG) targets the Trophoblast Antigen 2 (TROP2) receptor and has been shown to be effective in triple-negative breast cancer and hormone receptor-positive, HER2-negative advanced breast cancer. Fatigue, nausea, and diarrhea are the most common. Some ADCs have their own side effects. T-DXd, which can cause interstitial lung disease, and SG, which increases the risk of diarrhea. Monitoring and controlling these adverse events is important to achieve good patient outcomes. There are ongoing issues with ADC use including drug-related and other issues. The drug-related issues include side effects and ADCs drug resistance. This resistance can be due to a variety of reasons including downregulation of the target antigen, reduced internalization, increased drug efflux, and reduced burden. Strategies to reduce resistance include the use of combination therapies, early detection of resistance, and the development of more effective products. Second-generation ADCs with improved structure and potency are under development. There is ongoing research focusing on novel targets beyond HER2, such as Trop-2 and Claudin-18.2. Non-drug-related issues include tumor heterogeneity, patient selection, manufacturing issues, and increased costs. In conclusion, ADCs are a huge improvement over conventional chemotherapy for breast cancer treatment. The importance and use of ADCs in cancer treatment is bound to increase. The future of ADCs in breast cancer treatment looks promising with ongoing research into new targets, new therapeutic agents, and advances in drug resistance leading to mediated and effective methods.