Furthermore, the MEK1/2 inhibitor, AZD6244, was also able to synergise with AZD5363 in a range of HER2-amplified cell lines, suggesting that activation of ERK signalling in response to AZD5363 treatment may serve as a potential mechanism to limit its efficacy in HER2-amplified breast cancer lines. This evidence concerns the gene MAP2K1 and breast carcinoma.