Methods of treating or preventing chemoresistance or relapse growth of cancer cells are provided. Methods of treating or preventing resistance to tyrosine kinase based chemotherapeutic treatment in hematologic and solid tumors are provided. BCR-ABL drug resistance in chronic myelogenous leukemia (CML) and models for conducting further study on the same are presented. The methods comprise administering a therapeutically effective amount of one or more SIRT1 modulators to the cells or subject in need thereof. The methods may be administered in combination with, prior to or subsequent to chemotherapy or may be administered to counteract the effect of a spontaneous genetic mutation. Methods of using SIRT1 inhibitors to treat or prevent insulin and transferrin-induced resistance are also presented. A novel cell model to study mechanisms of acquired chemoresistance is also provided.
