Tumor-associated calcium signal transducer 2 (TROP2) (TROP2)

Tumor-associated calcium signal transducer 2 (TROP2), also known as Trophoblast antigen 2, is a 40 kDa type I transmembrane glycoprotein encoded by the TACSTD2 gene (UniProt: P09758). It functions as a calcium signal transducer and plays a pivotal role in regulating cellular proliferation, migration, and survival, primarily through the activation of the MAPK/ERK and PI3K/Akt signaling pathways (PubMed: 32809371). While TROP2 is expressed at low levels in various normal epithelial tissues, it is significantly overexpressed in a wide range of solid tumors, including triple-negative breast cancer, non-small cell lung cancer, and urothelial carcinoma, where it often serves as a marker of poor prognosis and increased metastatic potential (PubMed: 35563439). This differential expression profile makes TROP2 a highly attractive target for antibody-drug conjugates (ADCs). LCB84 (JNJ-87035869) is a clinical-stage ADC that utilizes site-specific conjugation to link a TROP2-targeting antibody to a potent cytotoxic payload (LegoChem Biosciences, 2023). Upon binding to TROP2 on the surface of malignant cells, the ADC is internalized via receptor-mediated endocytosis, leading to the intracellular release of the payload and subsequent induction of apoptosis (ClinicalTrials.gov: NCT05942729).

Other names

TACSTD2Trophoblast antigen 2Membrane component chromosome 1 surface marker 1M1S1Gastrointestinal antigen 733-1GA733-1Epithelial glycoprotein-1EGP-1

Antibody-drug conjugate (ADC) binding to TROP2 on the cell surface, followed by receptor-mediated endocytosis and intracellular release of a cytotoxic payload (e.g., microtubule inhibitor or topoisomerase I inhibitor) leading to cell death.