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Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein that is overexpressed in a wide range of cancers and is associated with poor prognosis and aggressive tumor behavior. This review synthesizes current research on the function of TROP2 in cancer progression through bibliometric analysis, with a special emphasis on advances in the study of antibody-drug conjugates (ADCs) targeting TROP2. We examine the efficacy of targeted therapies against TROP2, in particular the use of sacituzumab govitecan (SG), and evaluate their clinical impact on the treatment of various cancers. Through recent studies and clinical trials, we analyze the clinical effects of TROP2-ADCs and explored the prospects for their application in different cancers, including combination therapies with other therapeutic approaches, studies of resistance mechanisms, and further exploration of TROP2 as a biomarker. This review aims to provide a concise overview of TROP2 applications in cancer therapy, emphasizing emerging trends and therapeutic strategies to provide direction for future research and clinical practice.
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http://dx.doi.org/10.1016/j.ejmech.2025.117863 | DOI Listing |
Cancer Immunol Res
September 2025
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.
Antibody-based therapies have revolutionized cancer treatment but have several limitations. These include: down-regulation of the target antigen; mutation of the target epitope; or in the case of antibody drug conjugates (ADCs), resistance to the chemotherapy warhead. Since TROP2-targeted therapy with ADCs yields responses in TROP2+ solid tumors but lacks the durability observed with other immunotherapy-based approaches, we developed novel TROP2-targeting chimeric antigen receptor (CAR) T cells as an alternative.
View Article and Find Full Text PDFFront Oncol
August 2025
Department of Lung Cancer Surgery, Department of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
TROP2, a transmembrane glycoprotein, is overexpressed and plays pivotal roles in diverse epithelial tumors. The differential expression of TROP2 between cancer and normal tissues offers distinct advantages in developing drugs targeting it. Thus, TROP2-targeted antibody-drug conjugates (ADCs), including datopotamab deruxtecan and sacituzumab govitecan, present considerable efficacy and safety in multiple cancers.
View Article and Find Full Text PDFMol Diagn Ther
September 2025
Division of Pathology, IEO, European Institute of Oncology IRCCS, Via G. Ripamonti 435, 20141, Milan, Italy.
Background And Objective: Sacituzumab govitecan, an anti-trophoblast cell surface antigen 2 (TROP2) antibody-drug conjugate, has been approved by both the US Food and Drug Administration and European Medicines Agency for patients with metastatic triple-negative breast cancer who have received two or more prior systemic therapies, including at least one of them for advanced disease. Although TROP2 evaluation is not required for patient selection, survival data from the ASCENT trial show improved response rates in patients with high TROP2 expression by immunohistochemistry. However, there is no standardized testing assay for these patients.
View Article and Find Full Text PDFCancer Res
September 2025
University of California, Los Angeles, Los Angeles, CA, United States.
Metastasis is the main cause of prostate cancer-associated deaths, highlighting the urgent need to determine the mechanisms underlying prostate cancer progression. TROP2 (also known as TACSTD2) is an oncogenic transmembrane surface protein that is highly expressed in metastatic prostate cancer. Naturally occurring cleavage of TROP2 leads to a release of the TROP2 extracellular domain (TECD) into the extracellular environment.
View Article and Find Full Text PDFGynecol Oncol
September 2025
Department of Obstetrics, Gynecology, and Reproductive Sciences Yale University School of Medicine, CT 06520, USA. Electronic address:
Background: Cervical cancer is one of the most prevalent and deadly cancers worldwide. Here we demonstrate the preclinical pharmacology of Dato-DXd, a TROP2-targeting antibody-drug conjugate (ADC), against primary cervical cancer cell lines and xenografts.
Methods: Primary cervical cancer cell lines with differential TROP2 expression were identified by flow cytometry.