The present invention provides methods and compositions for treating cancers using a combination of a CYP 1 7 inhibitor and an additional therapeutic agent which modulates the PBK/Akt/mTOR pathway. In one aspect, the invention provides methods for the treatment of a disorder in a human subject. In some embodiments, the disorder is a neoplastic disorder. In some embodiments, the neoplastic disorder is a cancer. In some embodiments, the method comprises administering to said subject a 17a-hydroxylase/C17,20-lyase inhibitor (CYP17 inhibitor) and an additional agent, wherein the additional agent is a PBK inhibitor and/or mTOR inhibitor.