Trophoblast cell-surface antigen 2, DNA topoisomerase 1, and Thymidylate synthase (TROP2 + TOP1 + TYMS)

TROP2 + TOP1 + TYMS represents a multi-target biomarker profile used in precision oncology to guide therapeutic selection for solid tumors, most notably triple-negative breast cancer (TNBC) [5, 17]. Trophoblast cell-surface antigen 2 (TROP2) is a transmembrane glycoprotein overexpressed in various epithelial cancers that serves as the primary target for antibody-drug conjugates (ADCs) such as sacituzumab govitecan [6, 16, 20]. DNA topoisomerase 1 (TOP1) is an essential enzyme for DNA replication and the specific intracellular target of the cytotoxic payloads (e.g., SN-38) delivered by TROP2-directed ADCs [14, 21]. Thymidylate synthase (TYMS) is a critical enzyme in the de novo synthesis of thymidylate and the primary target of antimetabolite chemotherapies like 5-fluorouracil (5-FU) and capecitabine [5, 18]. This combination of targets is frequently assessed in diagnostic panels, such as the Multiplex8+ test, to help clinicians differentiate between patients likely to benefit from TROP2-targeted ADC therapy versus those who may respond better to traditional fluoropyrimidine-based regimens [5, 17, 18]. By evaluating the expression of the cell-surface antigen (TROP2), the payload's enzymatic target (TOP1), and the alternative metabolic pathway target (TYMS), this profile enables a more personalized and effective therapeutic strategy in aggressive malignancies [20, 21].

Other names

TACSTD2TOP1TYMSTSTumor-associated calcium signal transducer 2Thymidylate synthetasehRS7 targetSN-38 target5-FU target

The mechanism involves a multi-pronged therapeutic approach: 1) TROP2-directed antibody-drug conjugates (ADCs) bind to the cell surface, undergo internalization, and release TOP1 inhibitors (e.g., SN-38) to induce DNA double-strand breaks and apoptosis [14, 21, 23]; 2) Direct inhibition of DNA topoisomerase 1 by camptothecin derivatives prevents DNA religation during replication [14, 18]; and 3) Inhibition of thymidylate synthase by antimetabolites disrupts the synthesis of dTMP, leading to DNA synthesis inhibition and 'thymineless' cell death [5, 18].