Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence.
Simon LinderMarlous HoogstraatSuzan StellooNils EickhoffKarianne SchuurmanHilda A de BarrosMaartje AlkemadeElise M BekersTesa M SeversonJoyce SandersChia-Chi Flora HuangTunc MorovaUmut Berkay AltintasLiesbeth HoekmanYongsoo KimSylvan C BacaMartin SjöströmAnniek ZaalbergDorine C HintzenJeroen de JongRoelof J C KluinIris de RinkClaudia GiambartolomeiJi-Heui SeoBogdan PasaniucA F Maarten AltelaarRené H MedemaFelix Y FengAmina ZoubeidiMatthew L FreedmanLodewyk F A WesselsLisa M ButlerNathan A LackHenk G van der PoelAndries M BergmanWilbert ZwartPublished in: Cancer discovery (2022)
Understanding how prostate cancers adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenomic plasticity toward prosurvival signaling and uncovered the circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel lead for therapeutic development. See related commentary by Zhang et al., p. 2017. This article is highlighted in the In This Issue feature, p. 2007.