Abstract
Antibody-drug conjugates represent a new class of highly potent antineoplastic drugs built by attaching a small molecule of an anticancer drug (payload) or another therapeutic agent to an antibody recognizing an epitope on the targeted cells. Trophoblast cell-surface antigen-2 (Trop-2) was originally described in trophoblasts and fetal tissues, but subsequently its overexpression has been demonstrated in various solid malignancies. Sacituzumab govitecan (SG), a conjugate of anti-Trop-2 antibody and SN-38 payload (an active metabolite of irinotecan), is the first in the class that has been clinically validated and approved by the Food and Drug Administration for the treatment of metastatic triple-negative breast (2020) and urothelial carcinomas (2021). In the current review, we summarize and critically appraise the most recent advances with regard to SG, emphasizing the predictive biomarker analysis.
Highlights
Trophoblast cell-surface antigen-2 (Trop-2) protein as a target for antibody-drug conjugates (ADC)Trop-2, is a product of the TACSTD2 gene located at 1p32.1 reviewed in Goldenberg et al [1]
The Trop-2 protein interacts with multiple cellular regulators, including Insulin-like growth factor 1, claudin-1, claudin-7, cyclin D1, and Protein kinase C [1]
We recently reported Trop-2 in ~20% of mammary neuroendocrine carcinoma (NEC) (Figure 1) [14]
Summary
Trophoblast cell-surface antigen-2 (Trop-2) protein as a target for antibody-drug conjugates (ADC)Trop-2 ( called epithelial glycoprotein-1, gastrointestinal antigen 733-1, membrane component surface marker-1, and tumor-associated calcium signal transducer-2), is a product of the TACSTD2 gene located at 1p32.1 reviewed in Goldenberg et al [1]. Trophoblast cell-surface antigen-2 (Trop-2) protein as a target for antibody-drug conjugates (ADC) Semir Vranic and Zoran Gatalica: Trophoblast cell-surface antigen-2 and cancer treatment in the majority of solid tumors and its association with a poor prognosis provided a good rationale to target Trop-2 for therapeutic purposes [8].
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