The long road to colorectal cancer therapy: searching for the right signals.

During the last 25 years, improvements in our understanding of signaling processes mediating tumor initiation, growth and dissemination have opened the door towards increasingly efficient, selective, but also complex therapeutic approaches. In parallel, the better characterization of altered signaling pathways in tumor cells, as well as the relationship between these alterations and the sensitivity of tumors to given compounds, have forced us to contemplate the use of biomarkers allowing patient selection and evaluation of treatment efficacy. Such biomarkers should become a corner stone for the success of a more rational and "personalized" clinical approach to colorectal cancer. Here we give an overview of the "signaling pathway-selective" compounds that are currently in use or under clinical development in the setting of colorectal cancer (CRC) and we discuss promising targets, based on our current knowledge of colorectal tumor cell biology, such as Src family, Wnt and Hegdehog signaling.