HEIDELBERG — A study published in the journal Nature identifies the cell membrane protein TROP2 as a marker for aggressive and treatment-resistant colorectal cancer cells. Researchers from the German Cancer Research Center (DKFZ) and the HI-STEM Stem Cell Institute conducted the study.

René Jackstadt served as the study director. The study found that tumors with high TROP2 expression showed an increased likelihood of developing metastases. Patients whose tumors exhibited high TROP2 expression had a greater risk of recurrence.

TROP2-positive cells displayed characteristics associated with early stages of intestinal development. These cells can act as an alternative stem cell population, initiating new tumors and establishing metastases. Laboratory experiments also showed that standard chemotherapies for colorectal cancer promoted the development of TROP2-expressing tumor cells.

The study demonstrated that combining standard chemotherapy with TROP2-targeted therapy reduced tumor growth and metastasis more effectively than either therapy alone in tumor organoids and mouse models. "TROP2 specifically marks the colorectal cancer cells that contribute most strongly to metastasis, disease recurrence, and poor prognosis," Jackstadt said. He added, "We have demonstrated here for the first time in colorectal cancer that the plasticity of tumor cells can be exploited therapeutically."

Antibody-drug conjugates designed to target TROP2 are already approved for clinical use in other types of cancer, including breast cancer. "By combining chemotherapy with TROP2 blockade, we can specifically target the cells that are primarily responsible for relapses and metastases," Jackstadt said. "Since the drugs targeting TROP2 are already approved, we were able to translate our laboratory results into clinical trials relatively quickly." Researchers from the German Cancer Research Center, Heidelberg University Hospital, and NCT Heidelberg are currently testing an antibody-drug conjugate against TROP2 in a Phase 2/3 clinical trial involving patients with advanced colorectal cancer.

Why It Matters

The identification of TROP2 as a marker for aggressive colorectal cancer and the demonstrated effectiveness of TROP2-targeted therapies in laboratory and mouse models suggest a potential new approach for treating a challenging form of cancer. Colorectal cancer cells expressing TROP2 are linked to metastasis and recurrence, indicating that targeting these cells could address aspects of disease progression. The ongoing clinical trial with advanced colorectal cancer patients aims to evaluate this therapeutic strategy.