ArticleThe Journal of biological chemistry2014
Ovarian cancer-associated mutations disable catalytic activity of CDK12, a kinase that promotes homologous recombination repair and resistance to cisplatin and poly(ADP-ribose) polymerase inhibitors.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 1 of them a synthesis that pooled it.
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Who cites it
118 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 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
- Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes.British journal of cancer · 2018Trial
- Secondary Somatic Mutations RestoringCancer discovery · 2017Trial
- PARP Inhibitor Sensitivity in Tumors Harboring Non-BRCA Homologous Recombination Gene Alterations: Current Evidence Across Ovarian, Breast, Prostate, and Pancreatic Cancers.International journal of molecular sciences · 2026Review
- Cyclin K condensates bridge CDK12 to phosphorylate and drive oncogenic YAP activation in hepatocellular carcinoma.Science advances · 2026Article
- Absence of synergistic effects by CDK12/13 inhibition in combination with cisplatin or olaparib in ovarian cancer cells.Scientific reports · 2026Article
- Biomarkers in metastatic castration-resistant prostate cancer for efficiency of immune checkpoint inhibitors.Annals of medicine · 2025Review
- Article
- New insights into the dule roles CDK12 in human cancers: Mechanisms and interventions for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- Transcriptional and epigenetic rewiring by the NUP98::KDM5A fusion oncoprotein directly activates CDK12.Nature communications · 2025Article
- Mechanistic Roles of Transcriptional Cyclin-Dependent Kinases in Oncogenesis: Implications for Cancer Therapy.Cancers · 2025Review
- Development of CDK12 as a Cancer Therapeutic Target and Related Inhibitors.Current cancer drug targets · 2025Review
- Suppression of ADP-ribosylation reversal triggers cell vulnerability to alkylating agents.Neoplasia (New York, N.Y.) · 2025Article
- The Clinical Pathological Characteristics and Prognostic Relevance of Homologous Recombination Repair Gene Mutations in Ovarian Cancer Patients: A Prospective Cohort Study.Obstetrics and gynecology international · 2025Article
- Synthetic Lethal Targeting of CDK12-Deficient Prostate Cancer with PARP Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Star wars against leukemia: attacking the clones.Leukemia · 2024Review
- CDK12 loss drives prostate cancer progression, transcription-replication conflicts, and synthetic lethality with paralog CDK13.Cell reports. Medicine · 2024Article
- Prostate Cancer: A Review of Genetics, Current Biomarkers and Personalised Treatments.Cancer reports (Hoboken, N.J.) · 2024Review
- Interplay between altered metabolism and DNA damage and repair in ovarian cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- Effects of combined use of ribociclib with PARP1 inhibitor on cell kinetics in breast cancer.Oncology letters · 2024Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the tumor suppressors BRCA1 and BRCA2, which encode proteins that are key participants in homologous recombination (HR) repair, occur in ∼20% of high grade serous ovarian cancers. Although only 20% of these tumors have mutations in BRCA1 and BRCA2, nearly 50% of these tumors have defects in HR. Notably, however, the underlying genetic defects that give rise to HR defects in the absence of BRCA1 and BRCA2 mutations have not been fully elucidated. Here we show that the recurrent somatic CDK12 mutations identified in ovarian cancers impair the catalytic activity of this kinase, which is involved in the transcription of a subset of genes, including BRCA1 and other DNA repair genes. Furthermore, we show that disabling CDK12 function in ovarian cancer cells reduces BRCA1 levels, disrupts HR repair, and sensitizes these cells to the cross-linking agents melphalan and cisplatin and to the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888). Taken together, these findings suggest that many CDK12 mutations are an unrecognized cause of HR defects in ovarian cancers.
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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.