Kulkarni et al. [54] have demonstrated that calpain confers resistance to trastuzumab and apoptosis in HER2-positive breast cancer cells (SKBR3), deregulating calpain in turn deregulates activation of HER2 and PTEN/AKT1, and inversely inhibiting calpain helps in overcoming resistance to trastuzumab. This evidence concerns the gene AKT1 and breast cancer.