TROP2-Targeted Therapeutics in Development to Treat Gastrointestinal Tumors

Overexpression of trophoblast cell surface antigen 2 (TROP2) has been identified in various malignancies. Antibody–drug conjugates (ADCs) targeting TROP2 with topoisomerase 1 inhibitor chemotherapy payloads are currently marketed in breast and lung cancer. TROP2 ADCs currently in use carry unique toxicities and come with specifics in supportive care therapy. TROP2 investigation is highly prevalent in current oncology, with multiple TROP2-targeting agents in the investigative pipeline for a vast array of malignancies. Combination strategies are also being explored. Gastrointestinal (GI) malignancies represent a heterogeneous group of cancers—with some of the most common malignancies and some with a high incidence of cancer-related deaths—in dire need of newer therapies. Early phase 1/2 data show a spark of activity in reports on colorectal cancer and gastroesophageal cancer. Studies are underway for targeting TROP2 in colorectal cancer, pancreatic cancer, biliary tract cancers, and gastroesophageal cancers. Discovering more targeted therapy in GI malignancies is of utmost importance. This review will focus on the current progress of TROP2-targeting therapies in GI investigations, and what lies ahead for the future.