Trophoblast cell-surface antigen 2 (TROP2) and DNA topoisomerase 1 (TOP1) (TROP2/TOP1)

Trophoblast cell-surface antigen 2 (TROP2) is a transmembrane glycoprotein that is significantly overexpressed in various epithelial malignancies, including breast, lung, and gastric cancers, where it acts as a calcium-dependent signal transducer to promote tumor growth and metastasis [1]. DNA topoisomerase 1 (TOP1) is an essential nuclear enzyme that regulates DNA topology by creating transient single-strand breaks, allowing for the relaxation of supercoiled DNA during replication and transcription [2]. The therapeutic targeting of the TROP2-TOP1 axis is primarily achieved through antibody-drug conjugates (ADCs), which utilize a TROP2-specific monoclonal antibody to deliver a potent topoisomerase 1 inhibitor payload directly into cancer cells [3]. Once the ADC binds to TROP2 and is internalized, the payload—often a camptothecin derivative—is released and binds to the TOP1-DNA covalent complex, preventing DNA ligation and causing lethal double-strand breaks [5]. This mechanism exploits the high expression of TROP2 on tumor surfaces to achieve selective cytotoxicity while sparing healthy tissues with lower TROP2 levels [4]. Clinical applications of this target system, such as sacituzumab govitecan, have demonstrated significant efficacy in treating refractory triple-negative breast cancer and urothelial carcinoma [3, 5].

Other names

TACSTD2GA733-1M1S1EGP-1TOP1DNA topoisomerase I

Antibody-drug conjugate (ADC) targeting Trophoblast cell-surface antigen 2 (TROP2) to deliver a DNA topoisomerase 1 inhibitor payload, which stabilizes the TOP1-DNA covalent complex, leading to double-strand DNA breaks and apoptosis.