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| Status |
Public on Sep 04, 2024 |
| Title |
AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer [RNA-seq: 22RV1] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease. CBP/p300 bromodomain inhibition enhances response to standard of care therapeutics. Functional studies, CBP/p300 cistrome mapping, and transcriptome in CRPC revealed that CBP/p300 regulates DDR. Further mechanistic investigation showed that CBP/p300 attenuation via therapeutic targeting and genomic knockdown decreases homologous recombination (HR) factors in vitro, in vivo, and in human prostate cancer (PCa) tumors ex vivo. Similarly, CBP/p300 expression in human prostate tissue correlates with HR factors. Lastly, targeting CBP/p300 impacts HR-mediate repair and patient outcome. Collectively, these studies identify CBP/p300 as drivers of PCa tumorigenesis and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed and DDR therapies.
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| Overall design |
Gene expression profiling by high throughput sequencing in human prostate cancer cells (cell lines 22RV1).
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| Contributor(s) |
Shafi AA, McNair CM |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Aug 27, 2024 |
| Last update date |
Sep 04, 2024 |
| Contact name |
Christopher McNair |
| E-mail(s) |
christopher.mcnair@jefferson.edu
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| Organization name |
Thomas Jefferson University
|
| Department |
Medical Oncology
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| Street address |
833 Chestnut Street Ste 1140
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19107 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL34281 |
Illumina NovaSeq X (Homo sapiens) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA1152964 |
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