ArticleCell death & disease2021
CRISPR screening identifies CDK12 as a conservative vulnerability of prostate cancer.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Overlapping gene dependencies for PARP inhibitors and carboplatin response identified by functional CRISPR-Cas9 screening in ovarian cancer.Cell death & disease · 2022Pooled it
- Super-enhancer landscape regulated by CDK12 drives retinoblastoma progression.British journal of cancer · 2026Article
- A lactylation-associated gene signature predicts prognosis in neuroblastoma and identifies RPS6KA6 as a candidate biomarker.BMC cancer · 2026Article
- CDK12 Inactivation Attenuates Prostate Cancer Progression by Inhibiting BNIP3-Mediated Mitophagy.Cell proliferation · 2026Article
- CRISPR screening redefines therapeutic target identification and drug discovery with precision and scalability.Journal of pharmaceutical analysis · 2026Review
- Integrative transcriptomic profiling reveals subtype-specific therapeutic vulnerabilities and resistance mechanisms in prostate cancer.BMC cancer · 2026Article
- Transcriptional and epigenetic rewiring by the NUP98::KDM5A fusion oncoprotein directly activates CDK12.Nature communications · 2025Article
- Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer.Translational oncology · 2025Review
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- CDK12-Mediated Phosphorylation of FOXA1 Promotes Prostate Cancer Progression via the MDM2-p53 Axis.Research (Washington, D.C.) · 2025Article
- Compromised CDK12 activity causes dependency on the high activity of O-GlcNAc transferase.Glycobiology · 2024Article
- CRISPR/Cas9 Technology Providing the Therapeutic Landscape of Metastatic Prostate Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Review
- GRIN3A: A biomarker associated with a cribriform pattern and poor prognosis in prostate cancer.Neoplasia (New York, N.Y.) · 2024Article
- The Art of Finding the Right Drug Target: Emerging Methods and Strategies.Pharmacological reviews · 2024Review
- Let's make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment.Cell biology and toxicology · 2024Review
- Cyclin-dependent kinase 12 deficiency reprogrammes cellular metabolism to alleviate ferroptosis potential and promote the progression of castration-resistant prostate cancer.Clinical and translational medicine · 2024Article
- CDK12 regulates angiogenesis of advanced prostate cancer by IGFBP3.International journal of oncology · 2024Article
- A Genome Wide CRISPR Screen Reveals That HOXA9 Promotes Enzalutamide Resistance in Prostate Cancer.Molecular and cellular biology · 2024Article
- Trans-Regulation of AlternativeCells · 2023Article
- Research progress of anticancer drugs targeting CDK12.RSC medicinal chemistry · 2023Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Androgen receptor (AR) signaling inhibitors provide limited survival benefits to patients with prostate cancer (PCa), and worse, few feasible genomic lesions restrict targeted treatment to PCa. Thus, a better understanding of the critical dependencies of PCa may enable more feasible therapeutic approaches to the dilemma. We performed a kinome-scale CRISPR/Cas9 screen and identified cyclin-dependent kinase 12 (CDK12) as being conservatively required for PCa cell survival. Suppression of CDK12 by the covalent inhibitor THZ531 led to an obvious anti-PCa effect. Mechanistically, THZ531 downregulated AR signaling and preferentially repressed a distinct class of CDK12 inhibition-sensitive transcripts (CDK12-ISTs), including prostate lineage-specific genes, and contributed to cellular survival processes. Integration of the super-enhancer (SE) landscape and CDK12-ISTs indicated a group of potential PCa oncogenes, further conferring the sensitivity of PCa cells to CDK12 inhibition. Importantly, THZ531 strikingly synergized with multiple AR antagonists. The synergistic effect may be driven by attenuated H3K27ac signaling on AR targets and an intensive SE-associated apoptosis pathway. In conclusion, we highlight the validity of CDK12 as a druggable target in PCa. The synergy of THZ531 and AR antagonists suggests a potential combination therapy for PCa.
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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.