This was achieved by using both in vitro and in vivo models, as we demonstrated that inhibition of IRE1α-endonuclease activity with 4μ8C can prevent chemoresistance by enhancing the cytotoxic effect of DOX by lowering the tumor cell's anabolic tone of biomolecules, including lipids, and depriving tumor cells from their energy reserves. Here, ERN1 is linked to neoplasm.