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Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the Western world, causing 655 000 deaths worldwide per year.1 The incidence of colon cancer is usually increased in developed countries, being seemingly linked with a sedentary lifestyle and a high caloric intake. The occurrence of colon cancer is slightly higher in men than in women and increases with age. Most cases occur between the sixth and the seventh decade of life, while cases before age 50 are uncommon, unless a family history of early colon cancer is present. Colorectal cancer originates from epithelial cells lining the gastrointestinal tract, which undergo sequential mutations in specific DNA sequences that disrupt normal mechanisms of proliferation and self-renewal. Such mutations, which can derive by inborn genetic aberrations, tobacco smoking, environmental carcinogens and chronic inflammatory states, drive the transition from healthy colonic epithelia to increasingly dysplastic adenoma and finally to colorectal cancer. Stem cells of the gastrointestinal tract represent the natural target of tumourigenic mutations, due to both their long life and their capacity for self-renewal. The hypothesis of stem cell-driven tumourigenesis in colorectal cancer has received substantial support from the recent identification and phenotypic characterisation of a subpopulation of colon cancer cells able to initiate tumour growth and to reproduce human colon carcinomas faithfully in mice. This review will discuss the aspects of stem cell biology that can contribute to explain tumour development in the particular context of colorectal cancer. First, we will consider the knowledge available on normal colon cancer stem cells and on the dynamics of colon development, which is crucial to understanding the process of tumourigenesis. Then, we will summarise the new discoveries about colon cancer stem cells and discuss their relevance to the diagnosis and treatment of colorectal carcinoma.
ADULT STEM CELLS: THE CURRENT PICTURE
Competing interests: None.
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