Pathogenesis of colorectal cancer

The development of colorectal cancer has been viewed as an ordered process in which three main phases can be identified: initiation, promotion and pro gression. There is definite proof that stable alterations of the structure or sequence of DNA (mutations) represent the initiating event; these are fo llowed by an uncontrolled expansion of the neoplastic clones which characte rizes tumoural growth. Several classes of genes have been identified (oncog enes, tumour suppressor genes and "mutator" genes) the alterations of which are important in the initiation as well as in the promotion and progressio n of tumours. Colorectal cancer: therefore, results from a series of geneti c changes which lead to the progressive and irreversible loss of normal con trol of cell growth and differentiation. Available evidence is consistent w ith the hypothesis that there are several molecular pathways underlying the passage from normal mucosa to colorectal carcinoma, thus explaining the ex istence of intestinal tumours with a different biological nature, which may represent specific targets for prevention and cure. Well-defined molecular pathways have been identified for: A) sporadic colorectal cancer ("Loss of heterozygosity pathway"); B) familial adenomatous polyposis and related po lyposis syndromes; C) hereditary non-polyposis colorectal cancer ("mutator genes/microsatellite instability pathway"); D) cancer developing in inflamm atory bowel diseases; E) familial colorectal cancer. Thus, there is consist ent and considerable evidence suggesting the existence of several biologica l pathways leading to the same phenotypical expression (i.e., colorectal ca ncer), and it is likely that additional pathways will be clarified in the f uture. From a practical point of view, tumours with a diverse biology might offer different and more effective preventive and curative approaches.