Search for novel target molecules for the effective treatment or prevention of colorectal cancer

Abstract

The 5-year survival rate is more than 70% for patients without distant metastasis, while it is 10-20% for those with distant metastatic disease, suggesting the essential development of effective perioperative therapy. In a combination of cetuximab and FOLFIRI, the rate of conversion to resectable liver metastases is about 30%, and oncogenic activation of intracellular signaling pathway downstream of epidermal growth factor receptor, like KRAS mutations, is an important mechanism of resistance to anti-epidermal growth factor receptor therapy. Other molecules in oncogenic signal transduction and microRNA are attracting attention as candidates for new molecular targets. A cancer stem cell theory has been advocated even in gastrointestinal tract cancer and thought to be involved in multidrug resistance via ATP-binding cassette transport and active DNA repair. Despite newly-devised therapeutic ways, curative treatment of advanced colorectal cancer (CRC) leading to development of prevention is still difficult. Currently, the most effective preventive strategy is endoscopic polypectomy. A most recent report showed removal of adenoma was conducive to a 77% lower risk for CRC after 10 years. However, another means of prevention needs to be developed for familial adenomatous polyposis and hereditary non-polyposis CRC. Adding to the micronutrients, several key molecules have been investigated as target candidates for chemoprevention. A deeper understanding of the biology of CRC has been expanded, which is resulting in the development of novel therapies.