2017; Ma et al. 2015). Tumor cells can adapt to AI therapy after exposure for certain time (adaptive resistance), for instance due to the upregulation of ER expression or activation of alternative pathways conferring the cells survival and proliferative capacity. Instead, de novo or pre-existing resistance refers to the presence of estrogen independent cells before therapy. For instance, cells carrying specific mutations of the ER that confer constitutive ligand-idependent activity (Jeselsohn et al. 2015), which might lead to clonal selection under anti-hormonal treatment. The gene discussed is ESR1; the disease is neoplasm.