Pathways that control colorectal tumorigenesis. Mutations in the APC/b-catenin pathway initiate the neoplastic process, resulting in small benign tumors (adenomas). These tumors progress, becoming larger and more dangerous, as mutations in other growth-controlling pathway genes (such as KRAS, BRAF, PIK3CA, or TP53) accumulate. The process is accelerated by mutations in stability genes. The genetic alterations that drive metastasis have not yet been identified with certainty. The top line indicates potential clinical applications of knowledge of these pathways.
Modified from Kinzler, K.W., and Vogelstein, B. 1996. Cell 87:159170.