PIK3CA and neoplasm: In conclusion, our study has untangled the mechanism underlying cancer cell-specific apoptotic response in ErbB2-addicted cells, revisited the individual roles of ErbB2 and ErbB3 receptors in tumour targeting and defined a new, as yet disregarded adaptive response operating via RAS-PI3K/AKT crosstalk, which leads to a desensitization towards current therapeutics.