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Oropharyngeal squamous cell carcinoma (OPSCC) presents prognostic and therapeutic challenges. Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein involved in oncogenic signaling pathways and has been explored as a therapeutic target in many solid tumors. This study aims to evaluate the prevalence and prognostic significance of TROP2 expression in OPSCC and explore its association with the tumor immune microenvironment composition. A cohort of 112 OPSCC patients from two high-volume cancer centers was retrospectively analyzed. TROP2 expression was assessed by immunohistochemistry and categorized into negative/low versus moderate/high. Transcriptomic analysis was performed in a subset of samples to explore immune microenvironment correlations. Survival analyses were conducted using Kaplan-Meier curves and Cox regression models. Moderate/high TROP2 expression was observed in 42 % of patients and was significantly associated with lower levels of smoking and alcohol exposure, reduced rates of perineural invasion, and fewer positive lymph nodes. Patients with moderate/high TROP2 expression demonstrated a trend toward improved overall survival (OS) (HR = 0.54, P = 0.07) and significantly prolonged disease-free survival (DFS) (HR = 0.46, P = 0.03). In TCGA validation Kaplan-Meier survival analysis demonstrated that patients with high TROP2 gene expression had significantly improved OS compared to those with low TROP2 expression (P = 0.012, HR = 0.361 [0.14-0.93]). Transcriptomic analysis revealed an enrichment of cytotoxic immune populations in tumors with high TROP2 expression. In OPSCC patients, high TROP2 expression was associated with more favorable pathologic characteristics, improved DFS, and a higher presence of cytotoxic immune cells in the tumor microenvironment.
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http://dx.doi.org/10.1016/j.oraloncology.2025.107634 | DOI Listing |
Front 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.
J Immunother Cancer
September 2025
The Comprehensive Breast Care Center, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, Shaanxi, China
Background: Triple-negative breast cancer (TNBC) represents a subtype of breast cancer with poorest prognosis due to limited effective targeted therapies. Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable efficacy in treating hematological cancers, but its application in TNBC requires further development. One major obstacle is the lack of suitable tumor-specific target in TNBC.
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