Cytomegalovirus infection is common in prostate cancer and antiviral therapies inhibit progression in disease models.

Metastatic prostate cancer is incurable, and new therapeutic targets and drugs are urgently needed. Viral infections are associated with several cancer types, but a link between viruses and prostate oncogenesis has not been established. Only recently, an association between human cytomegalovirus (CMV) seropositivity and increased risk of prostate cancer mortality was demonstrated. Here, we show that CMV infection is common in the normal prostate epithelium and in prostate tumor tissue, with 70-92% of tumors being infected. Additionally, we report that commonly studied prostate cancer cell lines are CMV infected. Loss-of-function experiments demonstrate that CMV promotes cell survival, proliferation, and androgen receptor signaling, identifying it as a therapeutic target in castration-sensitive and castration-resistant prostate cancer. Several anti-CMV pharmaceutical compounds in clinical use inhibited cell expansion in prostate cancer models both in vitro and in vivo. We conclude that CMV is common in prostate cancer, promotes core prostate cancer cell programs, and can be inhibited by well-tolerated drugs. These findings motivate investigation into potential clinical benefits of CMV inhibition in the treatment of prostate cancer.