Colorectal Carcinogenic Pathways and Chemotherapeutic Responsiveness : A Review - Colorectal Carcinogenic Pathways and Chemotherapeutic Responsiveness : A Review - Open Access Pub

DOI10.14302/issn.2574-4526.jddd-16-1321 Colorectal cancer is one of the most common malignancies encountered in the western world and is now the third most common cause of cancer related mortality1. Indeed, such statistics are not limited to the western world as similar observations have been made in Asia where the incidence of colorectal cancer is rising. The growing size of the problem has necessitated the importance of continued research into this field that would not only lead to an enhanced understanding but also impact on clinical practice2, 3. Research into the molecular mechanisms has led to advances in therapies targeted at various molecular pathways4. Apart from unravelling the complexities of carcinogenesis, it has also enabled clinicians to predict response to chemotherapy. The translation of this research into clinical practice means that we are closer to developing individualised therapies for patients. This is also of considerable relevance as targeted individualised therapies would mean that the patients are less likely to suffer from any adverse side effects of treatment. In this review, a brief survey of the various molecular pathological mechanisms underlying colorectal carcinogenesis is presented. In the context of this approach, the response of patients to the various therapies is described. A brief description of the novel approach of molecular pathological epidemiology is also presented. A pubmed search was performed for relevant literature using the terms colorectal cancer, chemotherapy, molecular biology colorectal cancer, monoclonal antibodies, colorectal cancer genetics, pharmacogenetics of colorectal cancer. The bibliographies of the retrieved papers were also searched for articles of relevance. The Adenoma-Carcinoma Sequence and Molecular Pathways Histological observations indicated that colorectal malignancies develop via a worsening degree of dysplasia of normal colonic mucosa5. Fearon & Vogelstein proposed the adenoma- Carcinoma model of carcinogenesis which has undergone various modifications as precise molecular Details have been elucidated6. Colorectal cancer has been found to be a heterogeneous disease with four main aetiological pathways - the Chromosomal Instability pathway (CIN), cpg Island Methylator Phenotype (CIMP) pathway, Microsatellite Instability (MSI) pathway and the Serrated pathway7.8, 9, 10. A very brief description of these pathways and several other molecular mechanisms is described in the following paragraphs and also lay the foundation for a better understanding of the molecular pharmacology of the