Colorectal cancer is the third most common cancer in the United States and the second leading cause of all cancer-related deaths. Despite advances in our understanding into the mechanisms that induce colon cancer formation, treatment outcomes are still not very successful. Recently, neutral ceramidases (nCDase) was identified as a therapeutic target for the treatment of colon cancer; with nCDase KO mice displaying marked decreases in adenoma and adenocarcinoma formation in an AOM-induced mouse model of colon cancer. Current substrate mimetics for nCDase exhibit undesirable pharmaceutic properties for systemic delivery; consequently, there is a lack of specific inhibitors with pharmaceutical properties suitable for in vivo studies; impeding their study as a viable cancer target. The specific objective of this proposal is to utilize high- throughput screening (HTS) to identify chemical compounds that modulate nCDase activity and can be used to advance future in vivo studies as a potential therapeutic target.
Despite advances in our understanding into the mechanisms that induce colon cancer formation, approximately one third of patients die of disease. Recently, neutral ceramidases (nCDase) was identified as a therapeutic target for the treatment of colon cancer; with nCDase knockout mice displaying marked decreases in colon adenocarcinoma formation. The specific objective of this proposal is to utilize high- throughput screening to identify chemical compounds that modulate nCDase activity and can be used to advance future in vivo studies as a potential therapeutic target.
