Research Progress and Challenges in the Use of TROP2-Targeted Antibody-Drug Conjugates for the Treatment of Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, has long been associated with limited treatment targets, a high risk of recurrence and metastasis, and a poor prognosis. In recent years, antibody-drug conjugates (ADCs), which link targeted antibodies to cytotoxic payloads, have provided a new avenue for breakthroughs in precision therapy for TNBC. TROP2 is highly expressed in various epithelial tumors and is associated with tumor invasion, metastasis, and poor prognosis; it has thus become a key target for TNBC-ADC drug development. Existing studies indicate that TROP2-ADCs, represented by Sacituzumab Govitecan (SG), can improve treatment outcomes for patients with advanced TNBC; however, challenges remain, including unclear mechanisms of resistance, a lack of biomarkers, difficulties in managing adverse reactions, and insufficient evidence for specific patient populations. Future efforts should focus on further optimizing ADC structures, refining TROP2 detection standards, and exploring personalized combination therapy strategies to advance the development of precision medicine for TNBC. This article provides a review of the fundamental mechanisms, clinical research progress, challenges in clinical application, and future directions for TROP2-ADC drugs in the treatment of TNBC.