Links between biology, prognosis and prediction of response to chemotherapy in colorectal cancer.

Compared with the progress achieved in breast cancer, the use of prognostic and predictive parameters in colorectal cancer is lagging behind. One of the reasons is the limited information provided by 'classic' mutations as markers for response to therapy. To bridge this gap, prospective clinical trials need to be conducted to evaluate the usefulness of gene expression profiling and candidate markers, such as DNA repair proteins, onset of the methylator phenotype, neo-angiogenetic pathways related to inflammation, matrix metalloproteinases, tumor suppressors and cell signaling pathways (e.g. Akt). In parallel, the unrivalled sensitivity of molecular techniques may be applied to diagnostic parameters, such as cytokeratin 20 mRNA, for the detection of lymph node metastases. This article reviews the current knowledge on prognostic and predictive parameters in order to highlight the close link between tumor biology and tumor pharmacology. The increasing number of candidate markers together with recently introduced therapeutic options offer novel opportunities for a stepwise approach to the ambitious goal of individualized therapy in colorectal cancer.