Abstract: A combination therapy for the treatment of cancers refractory to anti-androgen therapy; particularly prostate cancer. The combination therapy includes a pharmaceutically effective amount of enzalutamide, bicalutamide, and/or abiraterone combination with ranolazine, perhexiline, and/or etomoxir. The invention also includes methods for treating cancer. The method can include the steps of administering to the subject a pharmaceutically effective amount of an anti-androgen drug in combination with a pharmaceutically effective amount of a drug that block or reduces lipid metabolism. The cancer can be prostate cancer. In a beneficial embodiment the prostate cancer is unresponsive or has a reduced responsiveness to anti-androgen treatment. The pharmaceutically effective amount of an anti-androgen drug can enzalutamide and abiraterone. It can also be combinations, analogs and derivatives of enzalutamide and/or abiraterone.