Notch and Wnt inhibitors as potential new drugs for intestinal neoplastic disease.
Colorectal cancer is a major cause of death in the western world. Recent advances in treatment comprise variations on the classical themes of surgical resection combined with chemotherapy using cytotoxic drugs and radiation therapy. Because this therapy is only moderately successful, novel approaches to the treatment of colorectal cancer are required. Our rapidly increasing knowledge of molecular signalling pathways that are deregulated in colorectal cancer might provide a platform from which to develop new rational cancer therapies. Here, we give an update on the roles of the Wnt and Notch signalling pathways in the self renewal of the intestinal epithelium and the consequences of Wnt deregulation in colorectal cancer. We focus on the potential of recently identified small-molecule inhibitors of the Wnt pathway and gamma-secretase inhibitors of the Notch pathway as novel colon cancer therapeutics.
van Es
Johan H
JH
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
Clevers
Hans
H
D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D010450:Endopeptidases / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007414:Intestinal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008954:Models, Biological; D051880:Receptors, Notch / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000235:genetics*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*; D051176:beta Catenin / Q000037:antagonists & inhibitors
D051880:Receptors, Notch; D051153:Wnt Proteins; D051176:beta Catenin; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human