Notch signaling and intestinal cancer.

In recent years, a substantial body of evidence has accumulated to support the notion that signaling pathways known to be important during embryonic development play important roles in regulating self-renewing tissues and tumorigenesis. In this context, Notch signaling is now recognized as essential for maintaining progenitor/ stem cell population as well as for regulating cell lineage differentiation in the normal intestinal mucosa. Many studies have also showed that Notch signaling is constitutively activated in colorectal cancer and its inhibition is able to suppress the cell growth and sensitize cancer cells to treatment-induced apoptosis. Therefore, discovery of the role of γ-secretase in the Notch signaling activation has prompted intensive research on the potential use of γ-secretase inhibitors in the treatment of colon cancer. This chapter reviews the current understanding and research findings of the role of Notch signaling in intestinal homeostasis and colorectal cancer and discusses the possible Notch targeting approaches as novel molecular therapy for intestinal cancer.