EpCAM As a Target in Cancer Therapy

TOTHEEDITOR: In their editorial, Schmoll and Arnold 1 discussed possible reasons for the ultimate failure of anti– epithelial cell-cell adhesion molecule (EpCAM) murine monoclonal antibody edrecolomab in the treatment of patients with colorectal cancer. 2-4 While we appreciate their analysis and conclusions, certain aspects are missing or need correction that may be important for the future development of anti-EpCAM therapies and better understanding of EpCAM as a target. Like for every targeted therapy, the level of EpCAM target expression will have an impact on the outcome of a trial. This was evident for the human anti-EpCAM antibody adecatumumab in patients with metastatic breast cancer. 5 Although a high level and frequency of EpCAM expression can be assumed for patients with colorectal cancer, 6 none of the previous trials prospectively or retrospectively analyzed patients for levels of EpCAM expression on tumor tissue. Particularly for a low-affinity antibody, such as edrecolomab, it may be of importance that tumor cells express EpCAM at a high and not just at an intermediate level. Even for the high-affinity antibody trastuzumab only patients with a high level ofHER2 target expression are eligible for treatment. Future studies will certainly benefit from stratifying patients for their level of EpCAM target expression.