Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer
Open Access
- 11 July 2021
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (14), 7431
- https://doi.org/10.3390/ijms22147431
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, p = 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 68Ga-PSMA after enzalutamide treatment (p = 0.004). Similarly, a clinical case with low baseline PSMA avidity demonstrated increased uptake of 68Ga-PSMA after enzalutamide on PET/CT and post-therapeutic 177Lu-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 177Lu-PSMA RLT.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (FE1573/3-1/659216)
- Mercator Research Center Ruhr (An-2019-0001)
- IFORES (D/107-81260, D/107-30240, n.a.)
- Doktor Robert Pfleger-Stiftung (n.a.)
This publication has 34 references indexed in Scilit:
- Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapyEJNMMI Research, 2015
- 68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human StudiesJournal of Nuclear Medicine, 2015
- Transcriptional response in normal mouse tissues after i.v. 211At administration - response related to absorbed dose, dose rate, and timeEJNMMI Research, 2015
- Synergistic co‐targeting of prostate‐specific membrane antigen and androgen receptor in prostate cancerThe Prostate, 2014
- Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigenProceedings of the National Academy of Sciences of the United States of America, 2011
- Correction: The Prostate Specific Membrane Antigen Regulates the Expression of IL-6 and CCL5 in Prostate Tumour Cells by Activating the MAPK Pathways1PLOS ONE, 2009
- The Prostate Specific Membrane Antigen Regulates the Expression of IL-6 and CCL5 in Prostate Tumour Cells by Activating the MAPK Pathways1PLOS ONE, 2009
- Prostate specific membrane antigen (PSMA) expression gives prostate cancer cells a growth advantage in a physiologically relevant folate environment in vitroThe Prostate, 2006
- Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancerJournal of Cellular Biochemistry, 2003
- Upregulation of prostate-specific membrane antigen after androgen-deprivation therapyUrology, 1996