Despite significant advances in medicinal sector breast cancer (BC) remains the major causes of cancer related death for women in USA and around the world. Different molecular signatures that drives BC are, amplification of ERBB2 expression, activation of hormone receptors such as estrogen (ER) and progesterone (PR) and BRAC mutations. Taking this heterogeneity into account, the treatment of BC requires molecular signature and molecular level understanding of the biology and molecular chemistry in different pathways such ER, ErbB2 and PI3K/AKT/mTOR. Here in Meilerlab we apply different state of art compuational methods to understand the mechanism of activation induced by genomic alterations of receptor protein specifically HER2. We simulatenously apply computational modeling in collaboration with cellular studies to understand the mechanism of resistance for different drug target with HER2 mutants.