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Theranostics 2024; 14(9):3674-3692. doi:10.7150/thno.98178 This issue Cite

Review

Trop2-targeted therapies in solid tumors: advances and future directions

Xinlin Liu^1,2, Leina Ma^1,2, Jiyixuan Li^1,2, Li Sun^1,2, Ying Yang^1,2, Ting Liu^1,2, Dongming Xing^1,2,3, Saisai Yan^1,2,✉, Miao Zhang^1,2,✉

1. The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China.
2. Qingdao Cancer Institute, Qingdao, 266071, China.
3. School of Life Sciences, Tsinghua University, Beijing, 100084, China.

✉ Corresponding authors: yss26edu.cn (S. Yan); zhangmiaoedu.cn (M. Zhang).

Abstract

Trophoblast cell surface antigen 2 (Trop2) is overexpressed in a range of solid tumors and participants in multiple oncogenic signaling pathways, making it an attractive therapeutic target. In the past decade, the rapid development of various Trop2-targeted therapies, notably marked by the advent of the antibody-drug conjugate (ADC), revolutionized the outcome for patients facing Trop2-positive tumors with limited treatment opinions, such as triple-negative breast cancer (TNBC). This review provides a comprehensive summary of advances in Trop2-targeted therapies, including ADCs, antibodies, multispecific agents, immunotherapy, cancer vaccines, and small molecular inhibitors, along with in-depth discussions on their designs, mechanisms of action (MOAs), and limitations. Additionally, we emphasize the clinical research progress of these emerging Trop2-targeted agents, focusing on their clinical application and therapeutic efficacy against tumors. Furthermore, we propose directions for future research, such as enhancing our understanding of Trop2's structure and biology, exploring the best combination strategies, and tailoring precision treatment based on Trop2 testing methodologies.

Keywords: Trop2, targeted therapies, solid tumor, therapeutic efficacy

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