Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Jul 24

PMID 34299051

Citations 21

Authors

Magdalena Staniszewska

Pedro Fragoso Costa

Matthias Eiber

Jasmin M Klose

Jasmin Wosniack

Henning Reis

Tibor Szarvas

Boris Hadaschik

Katharina Luckerath

Ken Herrmann

Wolfgang P Fendler

Janette Iking

Affiliations

Soon will be listed here.

Abstract

Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) prolongs overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, men with low PSMA expression are excluded from RLT. We explored the effect of androgen receptor blockade with enzalutamide on PSMA expression. Assessment of PSMA and androgen receptor (AR) expression on the human PC cell lines 22Rv1, C4-2, and LNCaP by immunohistochemistry and flow cytometry revealed low (22Rv1) and high (C4-2 and LNCaP) PSMA expression, and high, comparable AR positivity. Treatment with enzalutamide increased PSMA levels in 22Rv1, C4-2, and LNCaP (2.2/2.3/2.6-fold, = 0.0005/0.03/0.046) after one week compared to DMSO-treated controls as assessed by flow cytometry. NOD/Scid mice bearing 22Rv1 tumors were treated with enzalutamide for two weeks. Positron emission tomography/computed tomography (PET/CT) demonstrated higher tumor uptake of Ga-PSMA after enzalutamide treatment ( = 0.004). Similarly, a clinical case with low baseline PSMA avidity demonstrated increased uptake of Ga-PSMA after enzalutamide on PET/CT and post-therapeutic Lu-PSMA scintigraphy in a patient with mCRPC. Enzalutamide induced PSMA expression in the 22Rv1 xenograft model and in an mCRPC patient, both with low baseline tumoral PSMA levels. Therefore, enzalutamide pre-treatment might render patients with low PSMA expression eligible for Lu-PSMA RLT.

Citing Articles

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Prostate-Specific Membrane Antigen Biology and Pathophysiology in Prostate Carcinoma, an Update: Potential Implications for Targeted Imaging and Therapy.

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