High Intratumoral Dihydrotestosterone is Associated with Antiandrogen Resistance in VCaP Prostate Cancer Xenografts in Castrated Mice

Overview

Journal iScience

Publisher Cell Press

Date 2022 May 16

PMID 35573198

Authors

Riikka Huhtaniemi

Petra Sipila

Arttu Junnila

Riikka Oksala

Matias Knuuttila

Arfa Mehmood

Eija Aho

Teemu D Laajala

Tero Aittokallio

Asta Laiho

Laura Elo

Claes Ohlsson

Malin Hagberg Thulin

Pekka Kallio

Sari Makela

Mika V J Mustonen

Matti Poutanen

Affiliations

Soon will be listed here.

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.

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