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Trophoblast cell surface antigen 2 (TROP2) is a 40 kDa type I transmembrane glycoprotein that functions as a calcium signal transducer [UniProt: P09758]. Encoded by the TACSTD2 gene, it was originally identified in human placental trophoblasts and is known to play a critical role in regulating cell proliferation, migration, and survival through various signaling pathways, including MAPK/ERK and PI3K/AKT [PMID: 33035488]. While TROP2 expression is relatively low in normal adult epithelial tissues, it is significantly overexpressed in a wide range of solid tumors, such as breast, lung, and urothelial cancers [PMID: 32369232]. This high differential expression in malignant cells compared to healthy tissue makes TROP2 an ideal candidate for targeted cancer therapies. Currently, the most prominent therapeutic strategy involves antibody-drug conjugates (ADCs), such as sacituzumab govitecan, which bind to TROP2 to deliver potent cytotoxic agents directly into tumor cells [PMID: 34103323]. These therapies have shown significant clinical efficacy, particularly in patients with treatment-refractory advanced cancers [FDA: Trodelvy].
Antibody-drug conjugate (ADC) binding to the extracellular domain of TROP2, followed by receptor-mediated endocytosis and intracellular release of a cytotoxic payload (e.g., topoisomerase I inhibitor) to induce DNA damage and cell death [PMID: 34103323].
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