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Endocr Relat Cancer. 2018 Nov 1;25(11):R545–R557. doi: 10.1530/ERC-17-0136.

Molecular underpinnings of enzalutamide resistance

Author information

1
Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands
2
Laboratory of Molecular Endocrinology, KU Leuven, Leuven, Belgium
3
Department of Urology, University Hospitals Leuven, Leuven, Belgium
4
Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
5
Erasmus Optical Imaging Centre, Erasmus MC, Rotterdam, The Netherlands
6
Department of Biomedical Engineering, Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands

Abstract

Prostate cancer (PCa) is among the most common adult malignancies, and the second leading cause of cancer-related death in men. As PCa is hormone dependent, blockade of the androgen receptor (AR) signaling is an effective therapeutic strategy for men with advanced metastatic disease. The discovery of enzalutamide, a compound that effectively blocks the AR axis and its clinical application has led to a significant improvement in survival time. However, the effect of enzalutamide is not permanent, and resistance to treatment ultimately leads to development of lethal disease, for which there currently is no cure. This review will focus on the molecular underpinnings of enzalutamide resistance, bridging the gap between the preclinical and clinical research on novel therapeutic strategies for combating this lethal stage of prostate cancer.

KEYWORDS:

enzalutamide; abiraterone; resistance; androgen receptor; glycolysis; hexosamine biosynthesis; autophagy; cancer; prostate cancer; AKR3C1; Wnt; IL-6; mCRPC; mutations

PMID:
30306781
DOI:
10.1530/ERC-17-0136

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