Key clinical data and application prospects in breast cancer, gastric cancer, non-small cell lung cancer, and urothelial carcinoma are summarized and analyzed, while also delving into the challenges and future directions within this field.
Abstract
Human epidermal growth factor receptor 2 (HER2) and trophoblast cell surface antigen 2 (Trop-2) are tumor-associated antigens widely overexpressed in multiple malignant tumors, which drive malignant proliferation, invasion, metastasis, and therapeutic resistance by activating key downstream signaling pathways. Antibody–drug conjugates (ADCs) targeting HER2 and Trop-2 leverage their antigen-specific binding capacity to achieve precise targeted delivery of cytotoxic drugs, representing a significant breakthrough in solid tumor therapy. This review systematically outlines the biological functions and carcinogenic mechanisms of HER2 and Trop-2, focusing on the latest research and development progress of related ADCs. We also summarize and analyze key clinical data and application prospects in breast cancer (BC), gastric cancer (GC), non-small cell lung cancer (NSCLC), and urothelial carcinoma (UC), while also delving into the challenges and future directions within this field.
Next-generation ADCs may function not only as targeted cytotoxic agents but also as modulators of antitumor immunity in gastric cancer, and integrating tumor-antigen biology with immune-contextual features may enable more rational patient selection and therapeutic combinations.
Hong-Hua Su, Chun-Yin Yang, Jia-Yun Ge· Frontiers in Immunology· 0 citations
The rationale for targeting established and emerging antigens in non-small cell and small cell lung cancer, including HER2, TROP2, c-MET, HER3, CEACAM5, DLL3, and other promising targets currently under clinical investigation are discussed.
P. Paliogiannis, G. Fara, A. Zinellu et al.· Current Issues in Molecular...· 0 citations
GenSci139, an EGFR×HER2 bispecific ADC, is developed and demonstrated superior antitumor efficacy over DS-8201 in multiple cell-line-derived xenograft and patient-derived xenograft models, suggesting potential for synergistic combination with immunotherapies.
Xiaojuan Chai, Fu Li, Hongmei Xie et al.· Molecular Cancer Therapeutic...· 0 citations
The biological basis and translational challenges of de novo and acquired resistance related to targets, payloads, and tumor microenvironmental constraints, as well as the implications of these mechanisms for biomarker development, sequencing rationales, and combination strategies with immune checkpoint inhibitors and...
Chen-Xu Guo, L. Ellisen· Journal of Clinical Investig...· 0 citations
B7 homolog 3 protein (B7-H3, also known as CD276) has emerged as a promising immune checkpoint target because of its high expression in solid tumors, limited presence in normal tissues and roles in immune evasion and tumor progression. This review focuses on the biological and therapeutic relevance of B7-H3 in lung and...
Soorya Suresh, Surabhi Maurya, Kajal Singh et al.· Drug Discovery Today· 0 citations
TROP2-targeted antibody-drug conjugates (ADCs) have demonstrated promising clinical activity in triple-negative breast cancer (TNBC) as monotherapies; however, therapeutic benefit varies among patients. Combination strategies pairing TROP2-targeted ADCs with immune checkpoint inhibitors are also being investigated. Elu...
Sedat Dogru, A. Suresh, E. Bowman et al.· bioRxiv· 0 citations
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