Are there molecular targets for therapy of colon cancer?
Recent advances in understanding the molecular etiology of colorectal carcinoma have made possible a discussion of molecular targets for therapy of the disease. The genes for two inherited predispositions, familial adenomatous polyposis and the Lynch syndrome, have been mapped to specific chromosomal locations. At least five of the genes that are altered in structure or expression to give rise to the tumorigenic phenotype have been isolated by molecular cloning: The K-ras and N-ras protooncogenes have been shown to be altered by point mutation, and expression of the c-myc protooncogene is deregulated. The p53 and DCC genes, both tumor suppressor genes or antioncogenes, are deleted or altered so as to be rendered nonfunctional. Although a single tumor may not suffer all these changes, available evidence indicates that most colorectal tumors contain at least one of these alterations. In addition, work in cell culture and animal systems indicates that tumor cells may be converted to nonmalignant cells by reversing the effects of just one of these changes.
Astrin
S M
SM
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA.
D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000628:therapy*; D000818:Animals; D003001:Cloning, Molecular; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000628:therapy*; D016259:Genes, myc / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D051379:Mice