Endocrine Abstracts (2016) 42 OC16 | DOI: 10.1530/endoabs.42.OC16

Genomic analysis of Enzalutamide-resistant cells

Stefan Prekovic1, Thomas Van den Broeck1, Elien Smeets1, Martin van Royen2, Adriaan Houtsmuller2, Biswajyoti Sahu3, Päivi Pihlajamaa3, Olli A. Jänne3, Gerhardt Attard4, Frank Claessens1 & Christine Helsen1


1Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; 2Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands; 3Department of Physiology, University of Helsinki, Helsinki, Finland; 4The Institute of Cancer Research & Royal Marsden NHS Foundation Trust, London, UK


Enzalutamide (Enza) is a second-generation antiandrogen currently used in the clinic for treatment of metastatic prostate cancer. It significantly prolonged survival of men with metastatic castration resistant prostate cancer after chemotherapy by a median of 4.8 months in comparison to the placebo group. However, in a subset of patient’s beneficial effect of Enza cannot be observed, while others who initially respond eventually develop resistance towards the treatment. Understanding molecular pathways that mediate Enza resistance is important for future therapy and drug design. Thus, to study mechanisms that lead to resistance we generated Enza resistant LNCaP cells. The resistance to Enza was confirmed both in vitro, and in vivo in nude mice. Furthermore, we performed RNA sequencing, copy number analysis, FAIRE sequencing, and AR ChIP sequencing to study androgen receptor signaling and resistance mechanism. Our data provide a deeper insight into Enzalutamide resistance and point to specific mechanisms that occur in these resistant cells.

Support: FWO-Vlaanderen (G.0830.13N, FC), KU Leuven (GOA/15/017, FC), and Kom op tegen Kanker(FC).

Presenting Author: Stefan Prekovic, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000, Leuven, Belgium. Email: stefan.prekovic@med.kuleuven.be

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