Colorectal cancer, which includes primary cancer of the colon and rectum, is the third most common cancer in men and second for women in the world, based on GLOBOCAN statistics current at 2008. This accounts for 1.2 million new cases of colorectal cancer per year and 608,000 deaths attributed to this disease 1.
Several pathways are central to CRC carcinogenesis, the WNT signalling pathways being the most important. The tumour suppressor gene APC is frequently mutated, in a minority of cases β-catenin is mutated and in rare cases, functional analogues of APC like AXIN 1 and 2, NKD1 are the first step towards CRC. Consecutive steps towards the tumour development are the inactivation of additional tumour suppression genes in the p53 and TGFβ pathways. Activation of oncogenes such as KRAS, BRAF, and PI3CKA are necessary for the development of the tumour. Recent data from next generation sequencing demonstrate that in including these commonly affected genes and pathways a total number of 24 genes are repeatedly mutated in CRC but the frequency may differ between primary and metastasis 2.
Approximately 70-80% of newly diagnosed cases of CRC undergo curative resection, however 40% of these develop incurable recurrent disease due to undetected micrometastases 3. Patients with stage III (A, [T1,2N1M0] B [T3,4N1M0], C [TxN2M0]) have a 5-year survival rate of between 83% to 44%. Those with stage II (A [T3N0M0] or B [T4N0M0]) colon cancer after surgical resection have a 5-year survival rate of between 45–60% and 64–75%, respectively. The inability to cure all such patients is a direct consequence of residual occult disease. Adjuvant chemotherapy is offered to such high risk patients with the aim of decreasing relapse and improving overall survival (OS) by attempting to eliminate microscopic residual disease. Adjuvant therapy has been offered to patients with Stage III disease as standard therapy for over two decades, although the case of patients with Stage II disease the role of adjuvant therapy is controversial given the difficulty in identifying patients at the highest of risk who would benefit the most from adjuvant therapy.
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