Citation: European Journal of Cancer Supplements, Vol 7 No 2, September 2009, Page 17

A. Bardelli<sup>1

1</sup>The Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, University of Torino-Medical School, Candiolo (TO) and FIRC Institute of Molecular Oncology, Milan, Italy

Personalized cancer medicine based on the genetic milieu of individual colorectal tumors has long been postulated but until recently this concept was not supported by clinical evidence. The advent of the EGFR-targeted monoclonal antibodies cetuximab and panitumumab has paved the way to the individualized treatment of metastatic colorectal cancer (mCRC). There is clear evidence that mCRCs respond differently to EGFR-targeted agents and that the tumor specific response has a genetic basis. From the initial observation that cetuximab or panitumumab as monotherapy are effective only in 10–20%, of mCRCs, knowledge has being gained on the molecular mechanisms underlying primary resistance to these agents. The role of oncogenic activation of EGFR downstream effectors such as KRAS, BRAF, PIK3CA and PTEN on response to therapy will be discussed. The rapid and effective translation of these findings into predictive biomarkers to couple EGFR-targeted antibodies to the patients that benefit from them will be presented as a paradigm of modern clinical oncology. Unresolved questions such as understanding the molecular basis of response as well the mechanisms of secondary resistance will be discussed as the future fundamental goals in this research field.