Cancer Accumulation and Anticancer Activity of "CROX (Cluster Regulation of RUNX)" PIP in HER2-Positive Gastric Cancer Evaluated by Chicken Egg Cancer Model.

Background: We have focused on pyrrole-imidazole (PI) polyamide compounds, which preferentially bind to their target DNA sequences. To validate our "CROX (Cluster Regulation of RUNX)" strategy, we have created a novel PI polyamide-based inhibitor against RUNX termed Chb-M'. Recently, we have confirmed its cancer-specific uptake in mouse xenograft derived from HER2-positive gastric cancer cells. The accumulation and efficacy of Chb-M' in cancer has not yet been investigated in vivo, which is a simpler and less expensive method other than mouse xenograft models.

Methods: In the present study, we have employed the simple and versatile experimental system termed CAM (chorioallantoic membrane) model, and evaluated whether Chb-M' could have the cancer accumulation potential and anti-cancer activity.

Results: Based on our present results, gastric cancer MKN45 cells transplanted onto CAM successfully developed cancers, and the intravenously injected FITC-labeled Chb-M' obviously accumulated in these CAM cancers. As expected, the treatment of the CAM cancers with Chb-M' significantly attenuated the growth of the CAM cancers. Our present results were basically identical to those obtained from mouse xenograft model.

Conclusion: Our present findings strongly suggest that Chb-M' preferentially accumulates in cancer to suppress its growth, and the CAM model might serve as a valuable and promising platform to rapidly assess the cancer uptake and anti-cancer efficacy of various PI polyamide-based drug candidates.