HER3-targeting Antibody-drug Conjugates Therapy for Solid Tumors: Recent Advances and Future Potentials

Abstract: In most advanced cancers, standard medical treatments are generally employed. With the emergence of Antibody-Drug Conjugates (ADCs), more optimal therapeutic methods have become available for treating tumors. ADC is composed of a monoclonal antibody that targets a specific antigen and a cytotoxic payload, which conjugates via the synthetic linkers. Therefore, ADC combines the accurate targeting of monoclonal antibodies with the potent efficacy of cytotoxic chemotherapy drugs while circumventing systemic toxicity. Besides, the epidermal growth factor receptor (EGFR) family, expressing differently between tumors and normal tissues, is one of the most frequently targeted antigens for ADC therapy, which mainly encompasses EGFR1/ErbB1, human epidermal growth factor receptor 2/ epidermal growth factor receptor 2 (HER2/ErbB2), HER3/ErbB3, and HER4/ErbB4. In contrast to other targets, HER3 stands out as a promising one, closely associated with the pathogenesis of treatment resistance in several cancers. Moreover, solid tumors, which are more prevalent than hematological malignancies, present a vast field of opportunities for the development of HER3-targeting ADCs. However, research on HER3-targeting ADCs treating solid tumors remains insufficient. Therefore, it is imperative for researchers to gather more clinical trial data and continue to elucidate the efficacy and safety of HER3-ADCs in solid tumors. This review summarizes recent advances and future potentials, aiming to provide insights into targeted therapy. We hope that this review will provide useful information to physicians in the field.