The invention features methods for detecting prostate cancer, especially hormone-refractory prostate cancer (HRPC) or castration-resistant prostate cancer (CRPC), by detecting over-expression of PKIB or NAALADL2 compared the normal organs. Also disclosed are methods of identifying compounds for treating and preventing prostate cancer including HRPC, based on the over-expression of PKIB or NAALADL2 in the prostate cancer, the cell proliferation function of PKIB or NAALADL2, the intracellular localization of PKIB or NAALADL2 or the interaction between PKIB and PKA-C. Also, provided are a method for treating prostate cancer by administering a double-stranded molecule against the PKIB or NAALADL2 gene. The invention also provides products, including the double-stranded molecules and vectors encoding them, as well as compositions comprising the molecules or vectors, useful in the provided methods.