Methods for targeting adaptive responses to chemotherapy are described. In various embodiments, a method comprises administering at least one compound that inhibits S6K1, mTORC1 or upstream or downstream pathway components of S6K1 or mTORC1, in association with administration of at least one inhibitor of PPARα, PPARδ, or PGC1α. In various embodiments, the compound that inhibits S6K1, mTORC1, or upstream or downstream pathway components of S6K1 or mTORC1 is rapamycin, everolimus, temsirolimus, or imatinib. The inhibitor of PPARα, PPARδ, or PGC1α can be an antagonist or an inverse agonist selected from GW6471, GSK3787, GSK0660, and ST247.
