This might be due to the high intrinsic sensitivity of these models to lapatinib: accordingly, recent data show that, in colorectal cancer models, combined blockade of EGFR and MEK intercepts heterogeneous mechanisms of acquired resistance to anti-EGFR therapies and results in therapeutic synergism only once resistance to anti-EGFR agents has ensued [54, 58], suggesting that in highly sensitive models the right setting to apply combinatorial strategies might be treatment-resistant disease. Here, EGFR is linked to colorectal cancer.