Deregulation of apoptosis in colorectal carcinoma: theoretical and therapeutic implications

Apoptosis, or programmed cell death, maintains the structure of the colonic crypts by providing a balance to the rate of cell proliferation. Colorectal carcinoma arises partly from a disruption in this balance in the favour of uncontrolled growth. Until recently, most research into colon cancer has focused on the molecular regulators of cell-cycle progression and proliferation, but it is now evident that apoptosis is also defective. A failure of cells to die in response to premalignant damage may allow the progression of the disease and maintain the resistance of cancer cells to cytotoxic therapy. This review outlines the importance of apoptosis in the normal colon and presents recent studies that demonstrate that induction of apoptosis is defective in colonic tumours. When the molecular regulation of apoptosis is better understood, this knowledge may lead to the earlier detection of patients at greater risk of developing colorectal carcinoma, and also to the development of more effective therapies.