Colorectal Carcinogenic Pathways and Chemotherapeutic Responsiveness : A Review

ABSTRACT Colorectal cancer is one of the most common malignancies encountered in the developed world and its incidence has noted to be rising in the developing world as well. The considerable morbidity and mortality associated with this condition has driven research into elucidating the underlying molecular mechanisms in the hope that new therapeutic targets would be identified. This research has revealed the presence of distinct molecular pathways that culminate in malignant transformation of colorectal tissue. Mutations in several other pathways, most commonly involved in intracellular signalling have also been shown to act in conjunction with the distinct carcinogenic pathways and thereby predisposing to the development of cancer. These discoveries are beginning to have clinical applications as the identification of responders and non responders to particular chemotherapeutic agents is now possible to a certain extent via various molecular markers. In this paper, we briefly review the different carcinogenic pathways along with mutations in certain molecular pathways that aid the progression of malignant transformation. We also go on to discuss in detail, the different pharmacogenomic factors that influence a patient's response to various chemotherapeutic agents. Such knowledge not only would result in lower costs but would also minimise the exposure of patients to any undesirable side effects. These advances represent a step towards making personalised medicine a reality.