ORCID Profile
0000-0002-0861-5013
Current Organisations
Koç University
,
University of British Columbia
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Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.22541195
Abstract: Supplementary Data from Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.C.6549566
Abstract: Abstract In prostate cancer, androgen receptor (AR)–targeting agents are very effective in various disease stages. However, therapy resistance inevitably occurs, and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multiomics analyses on tissues isolated before and after 3 months of AR-targeting enzalutamide monotherapy from patients with high-risk prostate cancer enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors toward a neuroendocrine-like disease state. Additionally, epigenomic profiling revealed massive enzalutamide-induced reprogramming of pioneer factor FOXA1 from inactive chromatin sites toward active i cis /i -regulatory elements that dictate prosurvival signals. Notably, treatment-induced FOXA1 sites were enriched for the circadian clock component ARNTL. Posttreatment ARNTL levels were associated with patients’ clinical outcomes, and ARNTL knockout strongly decreased prostate cancer cell growth. Our data highlight a remarkable cistromic plasticity of FOXA1 following AR-targeted therapy and revealed an acquired dependency on the circadian regulator ARNTL, a novel candidate therapeutic target. Significance: 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. i a href="ancerdiscovery/article/doi/10.1158/2159-8290.CD-22-0702" target="_blank" See related commentary by Zhang et al., p. 2017 /a . /i i a href="ancerdiscovery/article/doi/10.1158/2159-8290.CD-12-9-ITI" target="_blank" This article is highlighted in the In This Issue feature, p. 2007 /a /i /
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.22541192
Abstract: Supplementary Figure from Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.22541195.V1
Abstract: Supplementary Data from Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.C.6549566.V1
Abstract: Abstract In prostate cancer, androgen receptor (AR)–targeting agents are very effective in various disease stages. However, therapy resistance inevitably occurs, and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multiomics analyses on tissues isolated before and after 3 months of AR-targeting enzalutamide monotherapy from patients with high-risk prostate cancer enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors toward a neuroendocrine-like disease state. Additionally, epigenomic profiling revealed massive enzalutamide-induced reprogramming of pioneer factor FOXA1 from inactive chromatin sites toward active i cis /i -regulatory elements that dictate prosurvival signals. Notably, treatment-induced FOXA1 sites were enriched for the circadian clock component ARNTL. Posttreatment ARNTL levels were associated with patients’ clinical outcomes, and ARNTL knockout strongly decreased prostate cancer cell growth. Our data highlight a remarkable cistromic plasticity of FOXA1 following AR-targeted therapy and revealed an acquired dependency on the circadian regulator ARNTL, a novel candidate therapeutic target. Significance: 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. i a href="ancerdiscovery/article/doi/10.1158/2159-8290.CD-22-0702" target="_blank" See related commentary by Zhang et al., p. 2017 /a . /i i a href="ancerdiscovery/article/doi/10.1158/2159-8290.CD-12-9-ITI" target="_blank" This article is highlighted in the In This Issue feature, p. 2007 /a /i /
Publisher: American Association for Cancer Research (AACR)
Date: 27-06-2022
DOI: 10.1158/2159-8290.CD-21-0576
Abstract: 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
Publisher: Wiley
Date: 10-07-2021
Abstract: Fauna surveys are traditionally manual, and hence limited in scale, expensive and labour‐intensive. Low‐cost hardware and storage mean that acoustic recording now has the potential to efficiently build scale in terrestrial fauna surveys, both spatially and temporally. With this aim, we have constructed the Australian Acoustic Observatory. It provides a direct and permanent record of terrestrial soundscapes through continuous recording across Australian ecoregions, including those periodically subject to fire and flood, when manual surveys are dangerous or impossible. The observatory comprises 360 permanent listening stations deployed across Australia. Groups of four sensors are deployed at each of 90 sites, placed strategically across ecoregions, to provide representative datasets of soundscapes. Each station continuously records sound, resulting in year‐round data collection. All data are made freely available under an open access licence. The Australian Acoustic Observatory is the world's first terrestrial acoustic observatory of this size. It provides continental‐scale environmental monitoring of unparalleled spatial extent, temporal resolution and archival stability. It enables new approaches to understanding ecosystems, long‐term environmental change, data visualization and acoustic science that will only increase in scientific value over time, particularly as others replicate the design in other parts of the world.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.22541192.V1
Abstract: Supplementary Figure from Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence
No related grants have been discovered for Umut Altintas.