INSR and breast carcinoma: However, NVP-AEW541 suffered from lack of efficacy and acquired resistance when tested against breast cancer cell lines.92 Challenges in targeting the IGF1R with ATP competitive inhibitors in oncology largely centre around lack of efficacy due to compensatory signalling from the other growth factors (including IR and hybrids), and side effects associated with inhibition of the IR.93 It follows that ATP competitive inhibitors would not be suitable for targeting the IR–IGF1R hybrid receptors, as these would simultaneously disrupt IR and IGF1R homodimer signalling.