Genetic pathways in colorectal and other cancers (Reprinted from Eur J Cancer, vol 35, pg 335-351, 1999)

Cells from cancers show aberrant behaviour such as unrestrained growth, inv asion into adjacent tissue and metastasis. All these features of cancer cel l behaviour can be explained in terms of genetic changes and the functional impact of these changes. In this review, colorectal cancer (CRC) is examin ed as a classical example of multistep carcinogenesis. First there is an ov erview which shows that cancers develop by a process of somatic evolution. This gives rise to preferred genetic pathways of tumorigenesis. The factors which may influence the development and ultimate choice of genetic pathway s are then examined. Next, CRC is studied as a specific disease and the put ative genetic pathways are described. The mutations that comprise these pat hways and the possible functional sequelae of these are explored. The revie w concludes with a look at those avenues which may further elucidate the na tural history of CRC and lead to improved therapy. (C) 1999 Elsevier Scienc e Ltd. All rights reserved.