Predictive and prognostic markers in colorectal cancer

Despite recent advances in the treatment of both early and advanced colorectal cancer, it remains the second leading cause of cancer deaths in the western world. There is, therefore, a pressing need to optimize the use of the currently available systemic therapies and to identify active new agents for the treatment of this disease. Pharmacogenomic studies have shown that genetically determined variability in key cellular functions can influence toxicity, response to treatment and survival. Numerous examples of these single 'classical' markers have been identified for a wide range of agents and each has been studied with regard to its effect on response. However, in any individual or tumor it is likely that a number of complex, interacting factors are involved in determining the likelihood of benefit with a given therapeutic agent. Microarray-based gene-expression profiling has allowed the complex range of molecular changes occurring in the cell and surrounding stroma to be assessed in relation to response and prognosis. Predictive gene sets have been developed and, along with other markers, are being assessed in prospective clinical trials. Treatment may soon be individualized by using this technology to predict which patients will benefit from a particular systemic therapy or which are likely to develop recurrence.