Since allelic loss or reduced expression of Rb in 25% to 50% of human prostate cancer [14, 35], and Pten deletion and/or mutations in 30% of primary prostate cancer and 63% of metastatic prostate cancer [15] were associated with more frequent clinical recurrence, Skp2 may serve an “Achilles' heel” type of drug target to effectively prevent or treat pRb and/or Pten deficient prostate cancer. The gene discussed is SKP2; the disease is metastatic prostate carcinoma.