Colorectal Cancer

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Colorectal cancer which involves the colon, rectum and the anal canal is the third most common malignancy worldwide. Induction of apoptosis process and inhibition of angiogenesis development are successful approaches to treat colorectal cancer. Apoptosis absconding and angiogenesis development in cancerous cells are consequences of up-regulating of number of pathways and proteins which controlled by oncogenes, or by down regulating of pathways which under control of tumor suppressor genes. Theses pathways including, p53, Wnt, hypoxia, NF kappa B, Notch , MAP kinase and other pathways are actually targets of the new anti-cancer agents (Ghobrial et al., 2005). Targeting one or more than of these pathways increases the selectivity of the chemotherapeutic agents as these pathways are only modulated in cancer cells rather than normal cells.

Most chemotherapeutic agents work via activation of apoptotic machineries. The frequency of apoptosis could contribute to cell loss in tumors and promote tumor regression (Naik et al., 1996). Apoptosis is accompanied by a series of morphological changes which include cell shrinkage, plasma and nuclear membrane blebbing, organelle relocalization and compaction, chromatin condensation, and production of membrane-enclosed particles containing intracellular material known as apoptotic bodies (Bold et al., 1997). An important fact of Colorectal cancer that it is highly angiogenic , besides it was the first tumor cell type to exhibit significant responses to anti-angiogenic agents both in vitro and in vivo (Mizukami and Chung, 2007). Angiogenesis research is the cutting edge technology that is currently being heavily exploited in the cancer field. Angiogenesis is a process of new blood vessel development orchestrated by a range of angiogenic factors and inhibitors. Angiogenesis plays an important role in cancer growth without which, tumors will be unable to expand beyond 1 to 2 mm3 (Folkman and Cotran, 1976). Cancer cells within the tumor will then use the newly formed blood vessels as a port to metastasize to other localities. Including the drugs for colon cancer, a growing number of anticancer agents have been shown to inhibit hypoxia inducible factor (HIF) gene activity. For many of these, the mechanism of action has been established and involves a reduction in HIF-1 mRNA or protein levels by suppressing the HIF gene expression (Semenza, 2007). Hypoxia is the principal trigger to stimulate VEGF gene transcription and subsequently to angiogenesis. VEGF is responsible triggering the various steps in the angiogenesis cascade such as proliferation, migration and cell survival.
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