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Colon cancer is a malignant tumor that begins in the large intestine (colon). The colon is the digestive tract's final section. Colorectal cancer is the third most common type of cancer in the Western hemisphere, with an increasing incidence as people age. Colorectal cancer is caused by environmental and genetic factors that promote the acquisition of cancer-specific behaviors in colon epithelial cells.
Currently, two distinct sequences ranging from normal colon to colorectal cancer have been identified. Both sequences involve the progression of normal colon epithelial cells to aberrant crypt foci, followed by early and advanced polyps, and finally advanced cancer. The 'traditional' or 'classic' path (top) involves the development of tubular adenomas that can progress to adenocarcinomas. An alternate pathway (bottom) has been described in the last 5–10 years that involves serrated polyps and their progression to serrated colorectal cancer. Each sequence contains genes that have been mutated or altered epigenetically. Certain genes are shared between the two pathways (for example, KRAS), while others are distinct (such as BRAF).
The progression of colorectal cancer is mediated by a number of well-defined genetic alterations, including mutations in APC, BRAF, KRAS, PIK3CA, p53, and FBXW7. We present several key targets involved in the mechanism of colorectal cancer in this section, including:
APC (adenomatous polyposis coli)
The function of APC (adenomatous polyposis coli) has been linked to the Wnt signaling pathway. APC can degrade -catenin and promote cellular adhesion, migration, and apoptosis under normal conditions. Due to the fact that APC deficiency is sufficient to initiate tumor development, APC mutations impair -catenin degradation, while truncated APC fragments promote colorectal cancer cell migration and induce chromosomal instability.
KRAS (Kirsten rat sarcoma viral oncogene homolog), a small GTPase involved in intracellular signal transduction and a member of the MAP kinase (MAPK) pathway . KRAS mutations contribute to KRAS protein activity deregulation, resulting in the loss of GTPase activity and the acquisition of oncogenic activity. Malignant transformation is caused by point mutations in exons 2 and 3 of the KRAS gene. Around 37.4 percent of Iranian patients with colorectal cancer have KRAS mutations.