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 patients 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: firstname.lastname@example.org