ArticleNucleic acids research2019
A novel CRISPR-engineered prostate cancer cell line defines the AR-V transcriptome and identifies PARP inhibitor sensitivities.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial.Nature medicine · 2024Trial
- Splicing factor TRA2B enhances synthesis of androgen receptor variant AR-V7 in prostate cancer cells.The Journal of clinical investigation · 2026Article
- Extracellular vesicle-mediated delivery of CRISPR machinery silences androgen receptor in castration-resistant prostate cancer cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Article
- The interconnection between androgen receptor and DNA damage response pathways in prostate cancer.Current urology · 2025Review
- Simultaneous inhibition of TRIM24 and TRIM28 sensitises prostate cancer cells to antiandrogen therapy, decreasing VEGF signalling and angiogenesis.Molecular oncology · 2025Article
- Targeting PCNA/AR interaction inhibits AR-mediated signaling in castration resistant prostate cancer cells.Oncotarget · 2025Article
- Defining Splicing Factor Requirements for Androgen Receptor Variant Synthesis in Advanced Prostate Cancer.Molecular cancer research : MCR · 2024Article
- Targeting mRNA-coding genes in prostate cancer using CRISPR/Cas9 technology with a special focus on androgen receptor signaling.Cell communication and signaling : CCS · 2024Review
- Review
- Loss of feedback regulation between FAM3B and androgen receptor driving prostate cancer progression.Journal of the National Cancer Institute · 2024Article
- ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer.Communications biology · 2024Article
- Androgen receptor, PARP signaling, and tumor microenvironment: the 'perfect triad' in prostate cancer?Therapeutic advances in medical oncology · 2024Review
- Review
- Synthetic Lethality by Co-Inhibition of Androgen Receptor and Polyadenosine Diphosphate-Ribose in Metastatic Prostate Cancer.International journal of molecular sciences · 2023Review
- The catalytic subunit of DNA-PK regulates transcription and splicing of AR in advanced prostate cancer.The Journal of clinical investigation · 2023Article
- The CDK7 inhibitor CT7001 (Samuraciclib) targets proliferation pathways to inhibit advanced prostate cancer.British journal of cancer · 2023Article
- A kinome-wide CRISPR screen identifies CK1α as a target to overcome enzalutamide resistance of prostate cancer.Cell reports. Medicine · 2023Article
- The Small Molecule Antagonist KCI807 Disrupts Association of the Amino-Terminal Domain of the Androgen Receptor with ELK1 by Modulating the Adjacent DNA Binding Domain.Molecular pharmacology · 2023Article
- Harnessing transcriptionally driven chromosomal instability adaptation to target therapy-refractory lethal prostate cancer.Cell reports. Medicine · 2023Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Resistance to androgen receptor (AR)-targeted therapies in prostate cancer (PC) is a major clinical problem. A key mechanism of treatment resistance in advanced PC is the generation of alternatively spliced forms of the AR termed AR variants (AR-Vs) that are refractory to targeted agents and drive tumour progression. Our understanding of how AR-Vs function is limited due to difficulties in distinguishing their discriminate activities from full-length AR (FL-AR). Here we report the development of a novel CRISPR-derived cell line which is a derivative of CWR22Rv1 cells, called CWR22Rv1-AR-EK, that has lost expression of FL-AR, but retains all endogenous AR-Vs. From this, we show that AR-Vs act unhindered by loss of FL-AR to drive cell growth and expression of androgenic genes. Global transcriptomics demonstrate that AR-Vs drive expression of a cohort of DNA damage response genes and depletion of AR-Vs sensitises cells to ionising radiation. Moreover, we demonstrate that AR-Vs interact with PARP1 and PARP2 and are dependent upon their catalytic function for transcriptional activation. Importantly, PARP blockade compromises expression of AR-V-target genes and reduces growth of CRPC cell lines suggesting a synthetic lethality relationship between AR-Vs and PARP, advocating the use of PARP inhibitors in AR-V positive PC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.