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. Colorecta l carcinoma arises partly from a disruption in this balance in the favour o f uncontrolled growth. Until recently, most research into colon cancer has focused on the molecular regulators of cell-cycle progression and prolifera tion, but it is now evident that apoptosis is also defective. A failure of cells to die in response to premalignant damage may allow die progression o f the disease and maintain the resistance of cancer cells to cytotoxic ther apy. This review outlines the importance of apoptosis in the normal colon a nd presents recent studies that demonstrate that induction of apoptosis is deflective in colonic tumours. When the molecular regulation of apoptosis i s;better understood, this knowledge may lead to the earlier detection of pa tients at greater risk of developing colorectal carcinoma, and also to the development of more effective therapies.