Overview of Trop-2 in Cancer: From Pre-Clinical Studies to Future Directions in Clinical Settings

SIMPLE SUMMARY: Trophoblast cell surface antigen-2 (Trop-2) is a widely expressed glycoprotein on a variety of different tumours. Trop-2 is considered as a marker of germ cells and is associated with regenerative ability in several tissues. Some studies demonstrated both oncogenic and tumour suppressor roles for Trop-2. In recent years, the therapeutic value of Trop-2 was identified and various studies with drug–antibody conjugates have been pursued in cancer patients. In this work, we reviewed both the pre-clinical and clinical activities of anti-Trop-2 therapy to highlight the future developments of these therapies. ABSTRACT: Trophoblast cell surface antigen-2 (Trop-2) is a glycoprotein that was first described as a membrane marker of trophoblast cells and was associated with regenerative abilities. Trop-2 overexpression was also described in several tumour types. Nevertheless, the therapeutic potential of Trop-2 was widely recognized and clinical studies with drug–antibody conjugates have been initiated in various cancer types. Recently, these efforts have been rewarded with the approval of sacituzumab govitecan from both the Food and Drug Administration (FDA) and European Medicines Agency (EMA), for metastatic triple-negative breast cancer patients. In our work, we briefly summarize the various characteristics of cancer cells overexpressing Trop-2, the pre-clinical activities of specific inhibitors, and the role of anti-Trop-2 therapy in current clinical practice. We also review the ongoing clinical trials to provide a snapshot of the future developments of these therapies.