Cytomegalovirus promotes proliferation and survival of prostate cancer cells and constitutes a therapeutic target

Classon, J.; Stenudd, M.; Zamboni, M.; Alkass, K.; Eriksson, C.-J.; Pedersen, L.; Schörling, A.; Thoss, A.; Bergh, A.; Wikström, P.; Adami, H.-O.; Sorensen, H. T.; Druid, H.; Frisen, J.

doi:10.1101/2023.10.01.560348

bioRxiv · 10.1101/2023.10.01.560348

Cytomegalovirus promotes proliferation and survival of prostate cancer cells and constitutes a therapeutic target

Classon, J.·Stenudd, M.·Zamboni, M.·Alkass, K.·Eriksson, C.-J.·Pedersen, L.·Schörling, A.·Thoss, A.·Bergh, A.·Wikström, P.·Adami, H.-O.·Sorensen, H. T.·Druid, H.·Frisen, J.

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Abstract

Metastatic prostate cancer is incurable and new therapeutic targets and drugs are needed. Viruses are associated with several cancer types, but their connection to prostate cancer is unclear. Here we show that human herpes virus cytomegalovirus (CMV) infection is common in the healthy prostate epithelium as well as in prostate cancer, with 85% of tumors being infected to varying degrees. The CMV gene locus UL122-UL123 upheld viral genome persistence in endogenously CMV infected prostate cancer cell lines. CMV promoted prostate cancer cell viability independently of androgen receptor status and anti-androgen resistance, partly through CMV UL97 and the androgen signaling pathway. DNA intercalation mitigated CMV infection and reduced CMV-dependent tumor size in xenotransplantation experiments. The anti-herpes drug aciclovir showed modest effects, but the well tolerated CMV UL97 kinase inhibitor maribavir partly mimicked CMV loss by inducing apoptosis and attenuating proliferation, resulting in reduced tumor growth in vivo. We conclude that CMV infects prostate cells in vivo and alters core prostate cancer cell properties, suggesting that it can be therapeutically targeted to improve prostate cancer outcomes.

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Classon, J., Stenudd, M., Zamboni, M., Alkass, K., Eriksson, C.-J., Pedersen, L., Schörling, A., Thoss, A., Bergh, A., Wikström, P., Adami, H.-O., Sorensen, H. T., Druid, H., Frisen, J.. 2023-10-01. Cytomegalovirus promotes proliferation and survival of prostate cancer cells and constitutes a therapeutic target. https://doi.org/10.1101/2023.10.01.560348

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