Biology of large bowel cancer

The progression of large bowel cancer from the colon crypt cell involves a series of sequential stages of altered growth regulation. An increase in the proliferative compartment of the colonic crypt characterizes the earliest stage. This is followed by loss of normal maturation and gain of more autonomous growth. Ultimately, cells that acquire the capability to migrate and grow at a distant site appear as metastases. Clinical and pathologic observations have been used to identify these stages of large bowel cancer progression, but only with the recent application of molecular and biologic tools are we beginning to identify potential mechanisms responsible for the altered growth. The development of laboratory models that reflect the key clinical and pathologic stages of progression should prove particularly valuable in sorting out the biology of large bowel tumor progression. The challenge then will be to use this knowledge for the design of preventive and therapeutic strategies.