@article{329922a8ea8b4ddc9f561a2a91952e3f,
title = "High intratumoral dihydrotestosterone is associated with antiandrogen resistance in VCaP prostate cancer xenografts in castrated mice",
abstract = "Antiandrogen treatment resistance is a major clinical concern in castration-resistant prostate cancer (CRPC) treatment. Using xenografts of VCaP cells we showed that growth of antiandrogen resistant CRPC tumors were characterized by a higher intratumor dihydrotestosterone (DHT) concentration than that of treatment responsive tumors. Furthermore, the slow tumor growth after adrenalectomy was associated with a low intratumor DHT concentration. Reactivation of androgen signaling in enzalutamide-resistant tumors was further shown by the expression of several androgen-dependent genes. The data indicate that intratumor DHT concentration and expression of several androgen-dependent genes in CRPC lesions is an indication of enzalutamide treatment resistance and an indication of the need for further androgen blockade. The presence of an androgen synthesis, independent of CYP17A1 activity, has been shown to exist in prostate cancer cells, and thus, novel androgen synthesis inhibitors are needed for the treatment of enzalutamide-resistant CRPC tumors that do not respond to abiraterone.",
keywords = "Cancer, Endocrinology",
author = "Riikka Huhtaniemi and Petra Sipil{\"a} and Arttu Junnila and Riikka Oksala and Matias Knuuttila and Arfa Mehmood and Eija Aho and Laajala, {Teemu D.} and Tero Aittokallio and Asta Laiho and Laura Elo and Claes Ohlsson and Thulin, {Malin Hagberg} and Pekka Kallio and Sari M{\"a}kel{\"a} and Mustonen, {Mika V.J.} and Matti Poutanen",
note = "Funding Information: Contributions from nonauthors:, Kim Petterson (University of Turku, Finland) kindly provided reagents for the PSA assay. The authors would like to thank the personnel of Turku Center for Disease Modeling (www.TCDM.fi) and the Histology Core Facility at the Institute of Biomedicine, University of Turku. The Turku Center for Disease Modeling is part of the Biocenter Finland Model Organisms Infrastructure. Funding sources:, The Academy of Finland, Cancer Society of Finland, Drug Research Doctoral Programme, Finnish Cultural Foundation, Orion Pharma, Sigrid Jus{\'e}lius Foundation, Swedish government, under the Agreement for Medical Education and Research, and the Swedish Research Council and University of Turku. Conceptualization, R.H. P.S. R.O. E.A. M.H.T. P.K. S.M. M.V.J.M. and M.P.; Methodology, R.H. M.K. P.K. S.M. and M.P.; Software, T.D.L. and T.A.; Validation, R.H. and M.P.; Formal Analysis, R.H. A.M. T.D.L. and T.A.; Investigation, R.H.; Resources, P.S. R.O. E.A. T.A. and M.P.; Data Curation, R.H. and M.P.; Writing – Original Draft, R.H. P.S. and M.P.; Writing – Review & Editing, R.H. P.S. R.O. M.K. A.M. E.A. T.D.L. T.A. M.H.T. P.K. S.M. M.V.J.M. and M.P.; Visualization, R.H. and A.M.; Supervision, P.K. S.M. and M.P.; Project Administration, R.H. and M.P.; Funding Acquisition, R.H. E.A. and M.P. R.O. and E.A. are employees and M.V.J.M. and P.K. are former employees of Orion Corporation, Orion Pharma. M.P. is a consultant of Forendo Pharma. The other authors declare no competing interests. Funding Information: The Academy of Finland , Cancer Society of Finland , Drug Research Doctoral Programme , Finnish Cultural Foundation , Orion Pharma , Sigrid Jus{\'e}lius Foundation , Swedish government , under the Agreement for Medical Education and Research , and the Swedish Research Council and University of Turku . Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = may,
day = "20",
doi = "10.1016/j.isci.2022.104287",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Cell Press",
number = "5",
}