Trophoblast cell-surface antigen 2 (TROP-2) (TROP-2)

Trophoblast cell-surface antigen 2 (TROP-2), also known as TACSTD2, is a 323-amino-acid transmembrane glycoprotein with an extracellular domain (274 amino acids including EGF-like and thyroglobulin type-1 repeats, 4 N-glycosylation sites), single transmembrane region, and cytoplasmic tail (containing PIP2 binding site and PKC-phosphorylatable serine at S303). It functions as a calcium signal transducer, promoting MAPK/ERK, NF-κB, and cyclin D1/E pathways to drive tumor proliferation, invasion, metastasis, and chemoresistance. Overexpressed in many epithelial cancers (e.g., TNBC, CRC, gastric) with low normal tissue expression, it is targeted by ADCs like sacituzumab govitecan (FDA-approved for TNBC/UC) and emerging CAR-T/NK therapies, though normal tissue expression poses toxicity risks.

Other names

tumor-associated calcium signal transducer 2 (TACSTD2)membrane component chromosome 1 surface marker 1 (M1S1)gastrointestinal antigen 733-1 (GA733-1)epithelial glycoprotein-1 (EGP-1)

Antibody-drug conjugate delivery of cytotoxins (e.g., SN-38) to TROP-2-expressing cells, CAR-T/NK cell activation for cytotoxicity (via CD28/4-1BB/CD3ζ or costimulatory domains like CD27), Pretargeting with bispecific antibodies for imaging/therapy, Internalization and calcium signaling disruption