Vertaisarvioitu alkuperäisartikkeli tai data-artikkeli tieteellisessä aikakauslehdessä (A1)
High intratumoral dihydrotestosterone is associated with antiandrogen resistance in VCaP prostate cancer xenografts in castrated mice
Julkaisun tekijät: Huhtaniemi R., Sipilä P., Junnila A., Oksala R., Knuuttila M., Mehmood A., Aho E., Laajala T.D., Aittokallio T., Laiho A., Elo L., Ohlsson C., Thulin M.H., Kallio P., Mäkelä S., Mustonen M.V.J., Poutanen M.
Kustantaja: Elsevier Inc.
Julkaisuvuosi: 2022
Journal: iScience
Tietokannassa oleva lehden nimi: iScience
Volyymi: 25
Julkaisunumero: 5
DOI: http://dx.doi.org/10.1016/j.isci.2022.104287
Verkko-osoite: https://doi.org/10.1016/j.isci.2022.104287
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/175577378
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
