Dual‑payload antibody‑drug conjugates in triple‑negative breast cancer: Preclinical advances and future perspectives (Review)

Triple-negative breast cancer (TNBC), a highly aggressive and challenging subtype of breast cancer, is distinguished by the absence of certain receptors, which affects the utilization of current treatment options.While some TNBCs could initially respond to chemotherapy, this approach is associated with high rates of recurrence and resistance mechanisms.In an effort to increase the selectivity and therapeutic efficacy of chemotherapy, antibody-drug conjugates (ADCs) have emerged to serve these purposes.However, tumor heterogeneity remains the major issue restricting their therapeutic effectiveness in TNBC, along with the emerging mechanisms of resistance associated with single-payload ADCs.The search for novel strategies is urgent.Dual-payload ADCs have been developed by incorporating two distinct payloads onto the same antibody to target a novel antigen overexpressed on TNBC, while also utilizing recent advances in the multi-target approach (bispecific antibodies) and chemoimmunotherapy to combat tumor heterogeneity, relapse and multiple mechanisms of resistance associated with TNBC.The present review summarizes the currently available preclinical dual-payload ADCs that target TROP2, CD276, EGFR and cMET, and future directions in an aim to provide a reference for researchers and facilitate further development.Notably, the most promising approach is TROP2-directed dual-payload ADCs, which could open new avenues in oncology.Contents 1. Introduction 2. Key design requirements of dual-payload ADCs 3. Mechanisms of action of dual-payload ADCs 4. Dual-payload ADCs in TNBC: Preclinical drugs and advancements 5. Therapeutic rationale and challenges of dual-payload ADCs in TNBC 6.Conclusion and future perspectives Dual-payload antibody-drug conjugates in triple-negative breast cancer: Preclinical advances and future perspectives (Review)