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.
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http://dx.doi.org/10.7150/thno.98178 | DOI Listing |
Mol Cancer Ther
December 2024
OBI Pharma, Inc., Taipei, Taiwan.
Trophoblast cell surface antigen 2 (TROP2) is highly expressed in multiple cancers relative to normal tissues, supporting its role as a target for cancer therapy. OBI-992 is an antibody-drug conjugate (ADC) derived from a novel TROP2-targeted antibody linked to the topoisomerase 1 (TOP1) inhibitor exatecan via an enzyme-cleavable hydrophilic linker, with a drug-antibody ratio of 4. This study evaluated and compared the antitumor activity of OBI-992 with that of benchmark TROP2-targeted ADCs datopotamab deruxtecan (Dato-DXd) and sacituzumab govitecan (SG) in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Extramammary Paget disease (EMPD) is a rare skin cancer that typically occurs in the anogenital area of older people. Since efficacy of treatments for metastatic or unresectable EMPD remains poor, development of a novel therapeutic approach is strongly desired. However, the lack of EMPD models has hampered investigation of EMPD.
View Article and Find Full Text PDFPathol Res Pract
December 2024
Department of Pathology, Cliniques universitaires Saint-Luc, Avenue Hippocrate 10, Brussels 1200, Belgium; Pôle de Morphologie (MORF), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue Hippocrate 10, Brussels 1200, Belgium.
J Nucl Med
December 2024
Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China;
Immuno-PET/CT imaging, a branch of molecular imaging, can noninvasively and specifically visualize biomarker expression across the body. Trophoblast cell surface antigen 2 (Trop2) is a pan-cancer biomarker and plays a crucial role in tumorigenesis through multiple signaling pathways. The study aims to develop and translate novel Trop2 single-domain antibody (sdAb) tracers for clinical use.
View Article and Find Full Text PDFMol Pharm
December 2024
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China.
Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein, plays a dual role in physiological and pathological processes. In healthy tissues, Trop2 facilitates development and orchestrates intracellular calcium signaling. However, its overexpression in numerous solid tumors shifts its function toward driving cell proliferation and metastasis, thus leading to a poor prognosis.
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