The title of my talk tomorrow will be acquired resistance to anti-EGFR therapy in colorectal cancer and how we’re going to manage that. In my short presentation I will briefly touch upon the main mechanisms of acquired drug resistance to anti-EGFR therapy in colorectal cancer patients then I will briefly discuss how tumour heterogeneity impacts the answer to secondary resistance. I’m going to just give a brief overview on how we can actually act upon some of the molecular mechanisms of drug resistance in colorectal cancer. For example, when EGFR secondary mutations occur in these patients we can actually act by re-challenging patients with newer antibodies that target these acquired resistance mutations. Or, for instance, we can apply different regimens, including drug holiday and discontinuations, to allow counter-selection of drug resistant tumour sub-clones and therefore re-challenge patients with the same therapy.

How is this applicable and does it have any clinical implications?

At the moment there’s a lot of debate in the community whether patients who benefit from a first line therapy containing anti-EGFR antibodies should be re-challenged with the same type of treatment in later lines of therapy, for example in third line. There have been no formal studies so far assessing this specific question and what I will present tomorrow is the preliminary data of a clinical trial that we have been conducting in this particular setting.