ArticleJournal of cancer research and clinical oncology2025
Expression and therapeutic potential of TROP2 in cisplatin-resistant germ cell tumors.
Article in Journal of cancer research and clinical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Comprehensive Profiling of Cell Surface Proteins in Testicular Germ Cell Tumors.Cancer research communications · 2026Article
- Biopsy RNA-seq captures TROP-2-linked migration and clonal resistance to forecast aggressiveness in metastatic melanoma.Journal of experimental & clinical cancer research : CR · 2026Article
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Authors and funding
13 authors.
Funding
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Abstract
BACKGROUND AND
objectivesCisplatin-based chemotherapy remains the standard of care for metastatic germ cell tumors (GCTs), but patients with cisplatin-refractory disease have limited effective options and poor outcomes. There is a clear unmet need for new therapies in this setting. Antibody–drug conjugates (ADCs) have emerged as a promising class of targeted agents for chemoresistant solid tumors. This study aimed to evaluate the expression of TROP2 in cisplatin-resistant GCT metastases [MET(-R)] and to assess the cytotoxic efficacy of the anti-TROP2 ADC sacituzumab govitecan (SG) in GCT cell lines.
methodsTROP2 mRNA and protein expression levels were analyzed in 31 post-chemotherapy viable MET(-R) specimens, including embryonal carcinoma (EC), choriocarcinoma (CC), yolk sac tumor (YST), and teratoma (TER), using quantitative reverse transcription polymerase chain reaction and immunohistochemistry with H-score evaluation. In vitro analyses included Western blotting and cell viability assays to assess TROP2 protein expression and SG-mediated cytotoxicity in GCT cell lines.
resultsTROP2 mRNA expression was significantly higher in post-chemotherapy CC- and TER-MET(-R) compared to YST-MET(-R) (p < 0.01). Immunohistochemistry showed moderate to strong membranous TROP2 expression in CC-MET(-R) [with H-score ≥ 100, median H-score 280 (interquartile range, IQR 225.0–298.0)] and TER-MET(-R) [median H-score 255 (IQR 200.0–265.0)]. Conversely, EC- and YST-MET(-R) showed absent or weak TROP2 expression [EC median H-score 22.5 (IQR 5.0–73.8); YST median H-score 0 (IQR 0–12.5)]. In vitro, SG induces dose-dependent cytotoxicity in TROP2-positive GCT cells, including cisplatin-resistant subclones (p < 0.01).
conclusionIn summary, TROP2 is variably expressed in cisplatin-resistant metastatic GCTs, with high expression most often seen in CC. SG shows strong cytotoxicity in TROP2-positive, chemotherapy-resistant GCT cells; however, its clinical effectiveness still needs to be confirmed.
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